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Applications of the Polymerase Chain Reaction to HLA Class II Typing

1992; Wiley; Volume: 63; Issue: 2 Linguagem: Inglês

10.1111/j.1423-0410.1992.tb02491.x

1423-0410

J. L. Bidwell,

Renal Transplantation Outcomes and Treatments

Of fundamental importance in the immune response are the human leucocyte antigen (HLA) genes, situated on chromosome 6 within the major histocompatibility complex (fig.la,b), HLA class I and class I1 genes encode transmembrane glycoproteins which present foreign antigenic peptides to T cells via T cell antigen receptor molecules.This cell-cell interaction triggers the immune response, resulting in proliferation of cytotoxic T cells, and antibody production and release by B cells.Apart from their role in peptide presentation, HLA antigens may trigger alloreactive immune responses following organ transplantation.Thus, mismatched HLA allotypes are a significant factor in allograft failure or rejection, in graft-versus-host and in host-versus-graft disease.For this reason, accurate HLA matching is usually a prerequisite in allogeneic transplantation.Until recently, HLA typing was dominated by serological and cellular techniques.Within the last 10 years, however, the analytical power of molecular biology has been applied with phenomenal success to the HLA system.As a result, allelic differences between HLA genes have been clearly defined at the nucleotide sequence level.At the same time, molecular probing techniques have enabled the rapid typing of these alleles.In particular, the HLA class I1 (DR, DQ and DP) genes have been the subject of'most interest, since DNA-based typing has proven considerably more accurate and reproducible than conventional serological or cellular typing.Concerted studies have revealed that most alloreactive epitopes of HLA class I1 antigens are located within membrane-distal protein domains, encoded by the second exon of the corresponding genes (fig.lc).