|
KMID : 0357119930150010119
|
|
Korean Journal of Immunology
1993 Volume.15 No. 1 p.119 ~ p.127
|
|
|
DNA Sequence of the HLA-DRB1 Chain from HLA-DR4 Subtype Alleles
|
|
Rhyu Mun-Gan
Lim Byung-Uk
Kim Gum-Ryong
|
|
|
Abstract
|
|
|
T lymphocytes recognize peptide antigens presented by human leukocyte antigen 9HLA) molecules which are characterized by extensive intraspecies allelic polymorphism, a phenomenon called major histsocompatibility complex (MHC) restricition. Thus HLA protein polymorphism may contribute to the specificity of T cell recognition by modulating direct interaction with the T cell antigen receptor (TCR) and peptide binding. Recently, a hypothetical class II foreign-antigen binding site was proposed.
This model predicted that antigens interact with class II polymorphic resdues constituting the inner surfaces of parallel α-helices and underlying, planar, B-pleated sheets of the foreign-antigen binding groove. Indeed, susceptiblitiy of certain
autoimmune disorders has been associated rhuematoid arthritis, whereas genetic susceptibility to pemphigus vulgaris appears associated with sequences in both DRB1 (DR4) locus and the DQB locus. The molecular basis of eleven DR4 subtypes resides in several nucleotide substitutions in the third hypervariable region of the DRB1 chain. Current methods for analysis of HLA class II alleles are limited by the time and effort redquired to make an dscreen either genomic or cDNA libraries. The polymerase chain reaction (PCR0 provides an approach that could eliminate these procedures and potentially speed up the acquisition of allelic sequences. We have therefore used a procedure for subtyping DR4-alleles that involves selective amplification of second exon of the DRB1 gene followed by hybridization with allele-specific oligonucleotide probe (ASO) or 2nd amplification with allele-specific oligonucleotide primer. The nucleotide sequences of in the third hypervariable region of the DR4 subtypes were also analysed with PCR amplified DNA. In Korean population, the most frequent DR4 subtypes is DRB1＊0405 which has been known to be significantly associated with autoimmune diseases. The third hypervariable region of DRB1＊0405 contains the same nucleotide sequences to DRB1＊0405 cntains the same nucleotide sequences to DRB1＊0101 that is also associated with autoimmune disease. Different nucleotide sequences between DRB1＊0405 and DRB1＊0101 located in the first hypervarible revion. Therefore it seems
like that the first hyyperdvariable region of HLA-DRB1 exon2 is implicated in allogeneicity, on the other hand the third hypervariable region is related with autoimmunity.
|
|
|
KEYWORD
|
|
|
Major Histocompatibility antigen, HLA-DR4, Allelic polymorphism
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
 
|