Immunobiology
Human Leukocyte Antigen and Its Role in Transplantation Biology

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Abstract

Human leukocyte antigens (HLA), the human version of the major histocompatibility complex (MHC), an integral part of maintenance of immune surveillance, have been widely studied for their roles in transplantation biology. A donor with an identical HLA system can donate tissue more successfully than the one who is not matched. The MHC is divided into class I, II, and III antigens; class I and II play important roles in transplantation immunology. HLA is codominantly expressed on chromosome 6 in every individual; HLA-A, -B, and -DR is known as the “haplo-type.” There are two sets of HLA antigens in each individual. Thus a child can inherit four different haplo-type combinations from parents. There is a 25% chance of totally matched or mismatched siblings and a 50% chance of half-matched siblings among a family with parents being a 50% match. The main purpose of HLA typing and lymphocyte crossmatching (LCM) in transplantation is to assess donor-recipient immune compatibility and identify the presence of preformed donor-specific cytotoxic alloantibodies in the recipient. It can be tested by serology or molecular techniques. We studied 8462 individuals for HLA typing by serology supplemented with molecular techniques (sequence-specific primers with low resolution). The common alleles were HLA-A19 (9.4%), -A1 (7.7%), -A2 (7.2%), -B5 (10.2%), -B35 (6.6%), -B40 (5.3%), -DR2 (10.2%), -DR5 (7.5%), and -DR7 (5.1%). HLA typing and LCM testing support successful transplantation.

Section snippets

Structure of MHC

MHC complex is divided into class I, II, and III on the basis of chemical structure and biologic properties (Fig 2). Class I and II play important roles in transplantation immunology. MHC class I is present on all nucleated cells, whereas class II is located only on the surface of certain cells like B lymphocytes, macrophages, dendritic cells, and tubular epithelial cells of the kidney. However, interferon-α can induce their expression on other cells like the T lymphocytes and endothelial

Cross-Reactivity

When two or more antigens share a similar structure, antibodies recognize them as the same structure while binding to them (eg, HLA-A1, -A36, -A11, and -A3 are cross-reactive alleles). This is also called CREG. In serological typing one must keep in mind these cross-reactive antigens.

HLA and Inheritance

HLA is codominantly expressed on chromosome 6 in every individual. According to the Mendelian law of inheritance, children inherit a set of HLA antigens from each of the parents, HLA-A, -B, and -DR, known as “haplo-type” (Fig 3). There are two sets of HLA antigens in each individual. Thus a child can inherit four different haplo-type combinations from parents. There is 25% chance of matched siblings, 50% chance of half match, and 25% chance of mismatched siblings in a family. However, each

Role of HLA Typing in Transplantation

HLA matching that reflects the immune reactivity of a host is more important for kidney and bone marrow transplantation than other organs. It has been clearly proved that better survival of a grafted kidney is achieved with better HLA matching. An antigen receptor of T lymphocyte interacts specifically with a composite ligand made up of peptide fragment of foreign protein bound to the peptide-binding groove of an MHC molecule. The physiological function of an MHC molecule is to present antigen

Methods of HLA Typing

The main purpose of tissue typing in transplantation is to assess donor-recipient compatibility for HLA and ABO and to analyze patient serum for antibodies that react with transplant donor tissues.

LCM

The methodology for LCM is similar to that of HLA serological typing except that the sera used will be those of recipients. In auto-crossmatch, the cells are subjected to their own sera for matching. In kidney transplantation, several modifications of the crossmatch assay have been used to increase its sensitivity, including anti-human globulin (AHG) augmentation, flow cytometry, enzyme-linked immunoassays, and B-cell crosshatches. Serum treatment with dithiothreitol (DTT) is used to

Demographics of HLA Alleles and LCM in Recipient-Donor Population of Western India (Table)

We routinely perform HLA typing by serology and supplemented it with molecular techniques (sequence-specific primers with low resolution). LCM is performed by flow cytometry and serology where we use AHG with additional Amos washing techniques, auto-crossmatch, T- and B-cell crossmatch at 4°C, 20°C, and 37°C each, and DTT to identify IgG antibodies (Table 1).

In our experience of HLA typing performed from January 1984 to September 2006 in 5021 individuals who were renal transplant recipients and

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