Biology Reference
In-Depth Information
ch 2
The HLA system in
hematopoietic stem cell
transplantation
Dominique Charron
Laboratoire “Jean Dausset”, Immunology-Immunogenetics-Histocompatibility, Université Paris-Diderot,
Hôpital Saint-Louis AP-HP, Paris, France
Effie Petersdorf
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
19
Introduction
Since the discovery of the HLA system [1,2] , there has been unprecedented
discovery of the gene number, structure and sequences, polymorphism,
haplotype composition and linkage disequilibrium (LD) within the MHC
[3] . More than 300 genes reside within the MHC and of these, approxi-
mately 15-20% have immune-related function including antigen process-
ing and presentation, immune regulation, inflammation, complement,
maternal-fetal immunology, stress response, leukocyte maturation and
the immunoglobulin superfamily [3] . New information on the regulatory
polymorphisms is emerging from efforts of the Human Epigenome Project
(HEP) and provides insight into methylation and histone acetylation pro-
files within the MHC [4,5] .
Classical HLA
Organization
The MHC is composed of three regions termed class I, class III and class II
( Figure 2.1 ). The HLA system includes the classical loci HLA-A, C and B, and
the non-classical genes HLA-E, HLA-F, HLA-G, MICA and MICB that reside
within the class I region. HLA-DR, HLA-DQ and DP reside within the class
II region. The class III region comprises genes of importance to the stress
response (TNF, HSP, LTA) and the complement cascade.
CLASS I
Class I HLA-A, -B and -C genes are each composed of a series of eight exons
delineated by intervening introns. Each class I exon has a unique function:
exon 1 encodes the leader sequence; exons 2, 3 and 4 encode the α1, 2 and
 
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