title: Effects of localized HLA class II beta chain polymorphism on binding of antigenic peptide and stimulation of T cells.
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.
authors.affiliation: Blood Center of Southeastern Wisconsin, Blood Research Institute, Milwaukee 53233.
authors.forename: D K
authors.initials: DK
authors.lastname: Newton-Nash
authors.forename: D D
authors.initials: DD
authors.lastname: Eckels
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000941:Antigens / Q000276:immunology*; D002460:Cell Line; D015798:HLA-DR1 Antigen / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; D015798:HLA-DR1 Antigen