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Effects of localized HLA class II beta chain polymorphism on binding of antigenic peptide and stimulation of T cells. Hum Immunol 1992 Mar;33(3):213-23

Date

03/01/1992

Pubmed ID

1618659

DOI

10.1016/0198-8859(92)90074-w

Scopus ID

2-s2.0-0026659773 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

The relationship between HLA-DR1 polymorphism and recognition of antigen by T cells was investigated. Two allelic variants of HLA-DR1, which differ by amino acid substitution at positions 85 and 86 of the beta chain, were characterized for the effect of substitution on recognition of foreign antigen by DR1-restricted T cells. Substitution of alanine and valine for valine and glycine residues at positions 85 and 86 of the DR1 beta chain resulted in deficient T-cell stimulation as demonstrated by the requirement for higher concentrations of antigen to induce maximal levels of T-cell proliferation, induction of lower levels of proliferation at optimal antigen concentrations, and slower kinetics of formation of stimulatory peptide-DR1 complexes. Direct binding studies employing both biotinylated and radioiodinated forms of antigenic peptide demonstrated quantitatively lower levels of peptide bound to substituted DR1 molecules and low levels of site-specific binding as assessed by competitive inhibition analyses. The effect of MHC class II polymorphism on peptide-binding affinity as opposed to induction of appropriate peptide conformation and the impact of polymorphism at DR1 beta chain positions 85 and 86 on allorecognition of HLA-DR1 are discussed.

Author List

Newton-Nash DK, Eckels DD

Author

Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of Wisconsin




MESH terms used to index this publication - Major topics in bold

Alleles
Amino Acid Sequence
Antigens
Cell Line
HLA-DR1 Antigen
Humans
Lymphocyte Activation
Molecular Sequence Data
Polymorphism, Genetic
T-Lymphocytes