Tissue Typing Education Primer

Part 1 of 6

Move to Part 2(Antigens), 3(Genetics), 4(Methods), 5(Relevance), 6(References)

THE HLA SYSTEM - INTRODUCTION

The term HLA refers to the Human Leucocyte Antigen System, which is controlled by genes on the short arm of chromosome six. The HLA loci are part of the genetic region known as the Major Histocompatibility Complex (MHC). The MHC has genes (including HLA) which are integral to normal function of the immune response. The essential role of the HLA antigens lies in the control of self­recognition and thus defence against micro­organisms.

The HLA loci, by virtue of their extreme polymorphism ensure that few individuals are identical and thus the population at large is well equipped to deal with attack.

Because some HLA antigens are recognised on all of the tissues of the body (rather than just blood cells), the identification of HLA antigens is described as "Tissue Typing".

HISTORY
The early development of HLA typing sprang from attempts by red cell serologists to define antigens on leucocytes using their established agglutination methods. These methods, however, were plagued with technical problems and a lack of appreciation for the extreme polymorphism of the system.

Although Jean Dausset reported the first HLA antigen, MAC (HLA­A2,A28) in 1958, the poor reproducibility of leuco-agglutination was hindering progress. It was five years later that the first glimpse of the polymorphic nature of the HLA system appeared. The definition of the 4a/4b series by Jan van Rood in 1963 and the definition of LA1, LA2 and LA3 (HLA-A1,HLA-A2, HLA­A3) by Rose Payne and Walter Bodmer in 1964 indicated a need for international standardisation and thus was born a series of International Workshops, starting in 1964. A summary of the events occurring at these workshops provides a chronicle of the milestones of achievement in HLA research:

1964 * Acceptance of Cytotoxicity over agglutination
1965 * Allelism of HLA antigens proposed
1967 * Segregation of Alleles demonstrated in families
1970 *"single" locus now two ­ HLA­A, HLA­B
1972 * 60 world populations typed by 75 laboratories
1975 * Third locus, HLA­C, demonstrated
1977 * HLA­D defined by Homozygous Typing Cells
........ * The serum-detected, D-related, HLA­DR defined
1984 * HLA and Disease associations explored
........ * Studies of gene structure
........ * World­wide Renal Transplantation data base
........ * Definition of MB (later to be HLA-DQ)
1987 * DNA techniques with serological, biochemical and cellular methods
........ * Definition of HLA­DP and HLA­DQ
1992 * Use of Polymerase Chain Reaction - eg for SSOP
1996 * Molecular definition of HLA-Class I
........ * Roles of HLA-G, E, DM, Tap & LMP's better understood

Move to Part 2(Antigens), 3(Genetics), 4(Methods), 5(Relevance), 6(References)