nach oben

Erschienen in:

01.05.2009 | Original Article

Relationship between CD8-dependent antigen recognition, T cell functional avidity, and tumor cell recognition

verfasst von: Tamson V. Moore, Gretchen E. Lyons, Natasha Brasic, Jeffrey J. Roszkowski, Simon Voelkl, Andreas Mackensen, W. Martin Kast, I. Caroline Le Poole, Michael I. Nishimura

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 5/2009

Einloggen, um Zugang zu erhalten

Abstract

Effective immunotherapy using T cell receptor (TCR) gene-modified T cells requires an understanding of the relationship between TCR affinity and functional avidity of T cells. In this study, we evaluate the relative affinity of two TCRs isolated from HLA-A2-restricted, gp100-reactive T cell clones with extremely high functional avidity. Furthermore, one of these T cell clones, was CD4⁻CD8⁻ indicating that antigen recognition by this clone was CD8 independent. However, when these TCRs were expressed in CD8⁻ Jurkat cells, the resulting Jurkat cells recognized gp100:209–217 peptide loaded T2 cells and had high functional avidity, but could not recognize HLA-A2⁺ melanoma cells expressing gp100. Tumor cell recognition by Jurkat cells expressing these TCRs could not be induced by exogenously loading the tumor cells with the native gp100:209–217 peptide. These results indicate that functional avidity of a T cell does not necessarily correlate with TCR affinity and CD8-independent antigen recognition by a T cell does not always mean its TCR will transfer CD8-independence to other effector cells. The implications of these findings are that T cells can modulate their functional avidity independent of the affinity of their TCRs.

Boon T, Coulie PG, Van den Eynde B (1997) Tumor antigens recognized by T cells. Immunol Today 18(6):267–268PubMedCrossRef

Rosenberg SA (1999) A new era for cancer immunotherapy based on the genes that encode cancer antigens. Immunity 10(3):281–287PubMedCrossRef

Mizoguchi H, O’Shea JJ, Longo DL, Loeffler CM, McVicar DW, Ochoa AC (1992) Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science 258(5089):1795–1798PubMedCrossRef

Finke JH, Zea AH, Stanley J, Longo DL, Mizoguchi H, Tubbs RR, Wiltrout RH, O’Shea JJ, Kudoh S, Klein E, Bukowski RM, Ochoa AC (1993) Loss of T-cell receptor zeta chain and p56lck in T-cells infiltrating human renal cell carcinoma. Cancer Res 53(23):5613–5616PubMed

Alexander-Miller MA, Leggatt GR, Berzofsky JA (1996) Selective expansion of high- or low-avidity cytotoxic T lymphocytes and efficacy for adoptive immunotherapy. Proc Natl Acad Sci 93(9):4102–4107PubMedCrossRef

Zeh HJ, Perry-Lalley D, Dudley ME, Rosenberg SA, Yang JC (1999) High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo antitumor efficacy. J Immunol 162(2):989–994PubMed

Dudley ME, Nishimura MI, Holt AK, Rosenberg SA (1999) Antitumor immunization with a minimal peptide epitope (G9–209–2 M) leads to a functionally heterogeneous CTL response. J Immunother 22(4):288–298PubMedCrossRef

Clay TM, Custer MC, Sachs J, Hwu P, Rosenberg SA, Nishimura MI (1999) Efficient transfer of a tumor antigen-reactive TCR to human peripheral blood lymphocytes confers anti-tumor reactivity. J Immunol 163(1):507–513PubMed

Duval L, Schmidt H, Kaltoft K, Fode K, Jensen JJ, Sorensen SM, Nishimura MI, von der Maase H (2006) Adoptive transfer of allogeneic cytotoxic T lymphocytes equipped with a HLA-A2 restricted MART-1 T-cell receptor: a phase I trial in metastatic melanoma. Clin Cancer Res 12(4):1229–1236PubMedCrossRef

10.

Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314(5796):126–129PubMedCrossRef

11.

Roszkowski JJ, Yu DC, Rubinstein MP, McKee MD, Cole DJ, Nishimura MI (2003) CD8 independent tumor cell recognition is a property of the T cell receptor and not the T cell. J Immunol 170(5):2582–2589PubMed

12.

Roszkowski JJ, Lyons GE, Kast WM, Yee C, Van Besien K, Nishimura MI (2005) Simultaneous generation of CD8⁺ and CD4⁺ melanoma reactive T cells by retroviral mediated TCR gene transfer. Cancer Res 65(4):1570–1576PubMedCrossRef

13.

Callender GG, Rosen HR, Roszkowski JJ, Lyons GE, Li M, Moore TV, Brasic N, McKee MD, Nishimura MI (2006) Identification of a CD8-independent Hepatitis C virus-specific T cell receptor that does not require CD8 for target cell recognition. Hepatology 43(5):973–981PubMedCrossRef

14.

Topalian SL, Solomon D, Rosenberg SA (1989) Tumor-specific cytolysis by lymphocytes infiltrating human melanomas. J Immunol 142(10):3714–3725PubMed

15.

Nishimura MI, Kawakami Y, Charmley P, O’Neil B, Shilyansky J, Yannelli JR, Rosenberg SA, Hood L (1994) T-cell receptor repertoire in tumor-infiltrating lymphocytes. Analysis of melanoma-specific long-term lines. J Immunother 16(2):85–94CrossRef

16.

Shilyansky J, Nishimura MI, Yannelli JR, Kawakami Y, Jacknin LS, Charmley P, Rosenberg SA (1994) T-cell receptor usage by melanoma-specific clonal and highly oligoclonal tumor-infiltrating lymphocyte lines. Proc Natl Acad Sci 91(7):2829–2833PubMedCrossRef

17.

Deveraux J, Haeberli P, Smithies O (1984) A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res 12(1):387–395CrossRef

18.

McKee MD, Roszkowski JJ, Nishimura MI (2005) T cell avidity and tumor recognition: implications and therapeutic strategies. J Transl Med 3:35PubMedCrossRef

19.

Kedzierska K, La Gruta NL, Davenport MP, Turner SJ, Doherty PC (2005) Contribution of T cell receptor affinity to overall avidity for virus-specific CD8+ T cell responses. Proc Natl Acad Sci 102(32):11432–11437PubMedCrossRef

20.

Trautmann L, Rimbert M, Echasserieau K, Saulquin X, Neveu B, Dechanet J, Cerundolo V, Bonneville M (2005) Selection of T cell clones expressing high-affinity public TCRs within Human cytomegalovirus-specific CD8 T cell responses. J Immunol 175(9):6123–6132PubMed

21.

Iero M, Squarcina P, Romero P, Guillaume P, Scarselli E, Cerino R, Carrabba M, Toutirais O, Parmiani G, Rivoltini L (2007) Low TCR avidity and lack of tumor cell recognition in CD8(+) T cells primed with the CEA-analogue CAP1–6D peptide. Cancer Immunol Immunother 56(12):1979–1991PubMedCrossRef

22.

Kim M, Moon HB, Kim K, Lee KY (2006) Antigen dose governs the shaping of CTL repertoires in vitro and in vivo. Int Immunol 18(3):435–444PubMedCrossRef

23.

Dudley ME, Wunderlich J, Nishimura MI, Yu D, Yang JC, Topalian SL, Schwartzentruber DJ, Hwu P, Marincola FM, Sherry R, Leitman SF, Rosenberg SA (2001) Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma. J Immunother 24(4):363–373PubMedCrossRef

24.

Koop BF, Rowen L, Wang K, Kuo CL, Seto D, Lenstra JA, Howard S, Shan W, Deshpande P, Hood L (1994) The human T-cell receptor TCRAC/TCRDC (C alpha/C delta) region: organization, sequence, and evolution of 97.6 kb of DNA. Genomics 19(3):478–493PubMedCrossRef

25.

Cole DJ, Weil DP, Shilyansky J, Custer M, Kawakami Y, Rosenberg SA, Nishimura MI (1995) Characterization of the functional specificity of a cloned T-cell receptor heterodimer recognizing the MART-1 melanoma antigen. Cancer Res 55(4):748–752PubMed

26.

Parkhurst MR, Salgaller ML, Southwood S, Robbins PF, Sette A, Rosenberg SA, Kawakami Y (1996) Improved induction of melanoma-reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0201-binding residues. J Immunol 157(6):2539–2548PubMed

27.

Seliger B (2008) Molecular mechanisms of MHC class I abnormalities and APM components in human tumors. Cancer Immunol Immunother. [Epub ahead of print]

28.

Seliger B, Ritz U, Ferrone S (2006) Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation. Int J Cancer 118(1):129–138PubMedCrossRef

29.

Ortmann B, Copeman J, Lehner PJ, Sadasivan B, Herberg JA, Grandea AG, Riddell SR, Tampé R, Spies T, Trowsdale J, Cresswell P (1997) A critical role for tapasin in the assembly and function of multimeric MHC class I-TAP complexes. Science 277(5330):1306–1309PubMedCrossRef

30.

Nishimura MI, Avichezer D, Custer MC, Lee CS, Chen C, Parkhurst MR, Diamond RA, Robbins PF, Schwartzentruber DJ, Rosenberg SA (1999) MHC class I-restricted recognition of a melanoma antigen by a human CD4+ tumor infiltrating lymphocyte. Cancer Res 59(24):6230–6238PubMed

31.

Theobald M, Biggs J, Dittmer D, Levine AJ, Sherman LA (1995) Targeting p53 as a general tumor antigen. Proc Natl Acad Sci 92(26):11993–11997PubMedCrossRef

32.

Kuball J, Schmitz FW, Voss RH, Ferreira EA, Engel R, Guillaume P, Strand S, Romero P, Huber C, Sherman LA, Theobald M (2005) Cooperation of human tumor-reactive CD4+ and CD8+ T cells after redirection of their specificity by a high-affinity p53A2.1-specific TCR. Immunity 22(1):117–129PubMedCrossRef

33.

Santomasso BD, Roberts WK, Thomas A, Williams T, Blachere NE, Dudley ME, Houghton AN, Posner JB, Darnell RB (2007) A T-cell receptor associated with naturally occurring human tumor immunity. Proc Natl Acad Sci 104(48):19073–19078PubMedCrossRef

34.

van den Boorn JG, Le Poole IC, Luiten RM (2006) T-cell avidity and tuning: the flexible connection between tolerance and autoimmunity. Int Rev Immunol 25(3–4):235–258PubMedCrossRef

35.

Jenkins MK, Schwartz RH (1987) Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med 165(2):302–319PubMedCrossRef

36.

Beverly B, Kang SM, Lenardo MJ, Schwartz RH (1992) Reversal of in vitro T cell clonal anergy by IL-2 stimulation. Int Immunol 4(6):661–671PubMedCrossRef

37.

Rosenberg SA, Spiess P, Lafreniere R (1986) A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233(4770):1318–1321PubMedCrossRef

38.

Aebersold P, Hyatt C, Johnson S, Hines K, Korcak L, Sanders M, Lotze M, Topalian S, Yang J, Rosenberg SA (1991) Lysis of autologous melanoma cells by tumor-infiltrating lymphocytes: association with clinical response. J Natl Cancer Inst 83(13):932–937PubMedCrossRef

39.

Alexander-Miller MA, Leggatt GR, Sarin A, Berzofsky JA (1996) Role of antigen, CD8, and cytotoxic T lymphocyte (CTL) avidity in high dose antigen induction of apoptosis of effector CTL. J Exp Med 184(2):485–492PubMedCrossRef

40.

Cawthon AG, Lu H, Alexander-Miller MA (2001) Peptide requirement for CTL activation reflects the sensitivity to CD3 engagement: correlation with CD8alphabeta versus CD8alphaalpha expression. J Immunol 167(5):2577–2584PubMed

41.

Cawthon AG, Alexander-Miller MA (2002) Optimal colocalization of TCR and CD8 as a novel mechanism for the control of functional avidity. J Immunol 169(7):3492–3498PubMed

42.

Lyons GE, Moore T, Brasic N, Li M, Roszkowski JJ, Nishimura MI (2006) Influence of human CD8 on antigen recognition by T-cell receptor-transduced cells. Cancer Res 66(23):11455–11461PubMedCrossRef

43.

Lyons GE, Roszkowski JJ, Man S, Yee C, Kast WM, Nishimura MI (2006) T-cell receptor tetramer binding or the lack there of does not necessitate antigen reactivity in T cell receptor transduced T-cells. Cancer Immunol Immunother 55(9):1142–1150PubMedCrossRef

44.

Gil D, Schrum AG, Alarcón B, Palmer E (2005) T cell receptor engagement by peptide-MHC ligands induces a conformational change in the CD3 complex of thymocytes. J Exp Med 201(4):517–522PubMedCrossRef

45.

Schamel WW, Risueño RM, Minguet S, Ortíz AR, Alarcón B (2006) A conformation- and avidity-based proofreading mechanism for the TCR-CD3 complex. Trends Immunol 27(4):176–182PubMedCrossRef

46.

Minguet S, Swamy M, Alarcón B, Luescher IF, Schamel WW (2007) Full activation of the T cell receptor requires both clustering and conformational changes at CD3. Immunity 26(1):43–54PubMedCrossRef

47.

Petersen TR, Gülland S, Bettelli E, Kuchroo V, Palmer E, Bäckström BT (2004) A chimeric T cell receptor with super-signaling properties. Int Immunol 16(7):889–894PubMedCrossRef

48.

Cohen CJ, Zhao Y, Zheng Z, Rosenberg SA, Morgan RA (2006) Enhanced antitumor activity of murine-human hybrid T-cell receptor (TCR) in human lymphocytes is associated with improved pairing and TCR/CD3 stability. Cancer Res 66(17):8878–8886PubMedCrossRef

49.

Kuball J, Dossett ML, Wolfl M, Ho WY, Voss RH, Fowler C, Greenberg PD (2007) Facilitating matched pairing and expression of TCR chains introduced into human T cells. Blood 109(6):2331–2338PubMedCrossRef

50.

Cohen CJ, Li YF, El-Gamil M, Robbins PF, Rosenberg SA, Morgan RA (2007) Enhanced antitumor activity of T cells engineered to express T-cell receptors with a second disulfide bond. Cancer Res 67(8):3898–3903PubMedCrossRef

51.

Voss RH, Willemsen RA, Kuball J, Grabowski M, Engel R, Intan RS, Guillaume P, Romero P, Huber C, Theobald M (2008) Molecular design of the Calphabeta interface favors specific pairing of introduced TCRalphabeta in human T cells. J Immunol 180(1):391–401PubMed

Titel: Relationship between CD8-dependent antigen recognition, T cell functional avidity, and tumor cell recognition
verfasst von: Tamson V. Moore
Gretchen E. Lyons
Natasha Brasic
Jeffrey J. Roszkowski
Simon Voelkl
Andreas Mackensen
W. Martin Kast
I. Caroline Le Poole
Michael I. Nishimura
Publikationsdatum: 01.05.2009
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 5/2009
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0594-2

Neu im Fachgebiet Onkologie

18.04.2024 | Wirbelsäulenmetastase | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Relationship between CD8-dependent antigen recognition, T cell functional avidity, and tumor cell recognition

Abstract

Neu im Fachgebiet Onkologie

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Adjuvante Brustkrebstherapie: Doppelt hält besser

Manche Gestagene können das Risiko für Meningeome erhöhen

Einladung zum PSA-Screening senkt die Krebssterblichkeit

Update Onkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2009

TCR transgenes and transgene cassettes for TCR gene therapy: status in 2008

The immunodominant HLA-A2-restricted MART-1 epitope is not presented on the surface of many melanoma cell lines

TNK cells (NKG2D+ CD8+ or CD4+ T lymphocytes) in the control of human tumors

HER-2/neu mediated down-regulation of MHC class I antigen processing prevents CTL-mediated tumor recognition upon DNA vaccination in HLA-A2 transgenic mice

Paradoxical concentration effect of a homodimerizing antibody against a human non-small cell lung cancer cell line

Effect of invariant chain on major histocompatibility complex class I molecule expression and stability on human breast tumor cell lines

Neu im Fachgebiet Onkologie

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Adjuvante Brustkrebstherapie: Doppelt hält besser

Manche Gestagene können das Risiko für Meningeome erhöhen

Einladung zum PSA-Screening senkt die Krebssterblichkeit

Update Onkologie