Recognition of altered self major histocompatibility complex molecules modulated by specific peptide interactions.
Antigen-specific and major histocompatibility complex (MHC)-restricted recognition by the T cell receptor involves multiple structural contacts over a large molecular surface area. Using a human T cell clone specific for a rubella viral peptide restricted by subsets of HLA DR4 molecules, we identified structurally diverse combinations of peptide-MHC complexes which were functionally equivalent to T cell recognition. Presentation of the rubella-derived peptide on DR4 molecules with an E-74 polymorphism triggered T cell recognition, as did presentation of a single amino acid-substituted peptide in the context of DR4 molecule which lacked the E-74 site. Peptide binding and molecular modeling analysis indicates the structural and functional complementarity of T cell recognition for a specific amino acid side chain, whether contributed by the peptide or by the MHC molecule.
Nepom
G T
GT
Virginia Mason Research Center, Settle, WA 98101, USA.
Ou
D
D
Lybrand
T P
TP
DeWeese
C
C
Domeier
M E
ME
Buckner
J H
JH
Mitchell
L A
LA
Tingle
A J
AJ
D000483:Alleles; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006801:Humans; D008213:Lymphocyte Activation; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000378:metabolism; D012409:Rubella / Q000276:immunology*; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*
D000956:Antigens, Viral; D001324:Autoantigens; D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014759:Viral Envelope Proteins; C061826:E1 envelope protein, Rubella virus