The role of polymorphic I-Ak beta chain residues in presentation of a peptide from myelin basic protein.
Proteins encoded by genes in the MHC are highly polymorphic. For class II proteins the highest level of polymorphism is found in distinct regions of variability, notably in the membrane-distal domains. To investigate the role of such residues in antigen presentation, we have tested cells transfected with wild-type or mutant I-Ak beta chains for their ability to present the NH2-terminal peptide of myelin basic protein to a panel of T cell clones. We were unable to detect a gross effect on peptide binding, in that all of the mutant cell lines presented antigen to at least one of the cloned T cells. However, the results imply that the more NH2-terminal residues, particularly 12 and 14, are involved in peptide interactions. Mutations at these residues presented antigen only at high antigen concentrations. Furthermore, residues of the more COOH-terminal regions appear to determine TCR interactions. Mutations in the predicted alpha-helical regions of the beta chain affected antigen presentation without abolishing peptide binding.
Davis
C B
CB
Department of Biological Sciences, Stanford University, California 94305.
Buerstedde
J M
JM
McKean
D J
DJ
Jones
P P
PP
McDevitt
H O
HO
Wraith
D C
DC
D000596:Amino Acids / Q000235:genetics; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D008213:Lymphocyte Activation; D051379:Mice; D008805:Mice, Inbred A; D009154:Mutation; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology
D000596:Amino Acids; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010446:Peptide Fragments