RESIDUE-67 IN THE DR-BETA-1-ASTERISK-0101 AND DR-BETA-1-ASTERISK-0103CHAINS STRONGLY INFLUENCES ANTIGEN PRESENTATION AND DR-PEPTIDE MOLECULAR-COMPLEX CONFORMATION

Citation
Fe. Lfaqihi et al., RESIDUE-67 IN THE DR-BETA-1-ASTERISK-0101 AND DR-BETA-1-ASTERISK-0103CHAINS STRONGLY INFLUENCES ANTIGEN PRESENTATION AND DR-PEPTIDE MOLECULAR-COMPLEX CONFORMATION, Tissue antigens, 51(1), 1998, pp. 10-19
Citations number
31
Categorie Soggetti
Pathology,Immunology,"Cell Biology
Journal title
ISSN journal
00012815
Volume
51
Issue
1
Year of publication
1998
Pages
10 - 19
Database
ISI
SICI code
0001-2815(1998)51:1<10:RITDAD>2.0.ZU;2-K
Abstract
Two closely-related molecules, DR(alpha,beta 10101) and DR(alpha,beta 10103), whose beta chains only differ by three amino acids at positi ons 67, 70, and 71, and six intermediate molecules obtained by site-di rected mutagenesis were used to ascertain the respective roles of the three polymorphic residues. Substitutions at positions 70 (D --> Q), 7 1 (E --> R) and 67 (I or L --> F) strongly affected HA 306-318-specifi c T-cell recognition. The consequences of the substitution of residue 67 by a phenylalanine depended on the modified HLA-DR molecule. Althou gh this substitution completely inhibited peptide-specific DR1-restric ted T-cell recognition, its manifestations on the DR103S-restricted T cell response were variable (abolishing proliferation of some cell lin es and not others), no matter what the peptide presented was (HA 306-3 19 or HIV P25 peptides). We also observed that inhibition of the proli feration of an alloreactive anti-DR103 T-cell clone, caused by a subst itution at position 70, was completely canceled by substitution oi res idue 67 by a phenylalanine. The observations based on functional exper iments, thus, suggest that residue 67 plays an important role in deter mining conformation of the peptide presented to the T cell. Molecular modeling was used io predict changes induced by amino acid substitutio ns and highly support-functional data. Substitution of residue 67 by a phenylalanine could have repercussions on the structure of HLA-DR mol ecule/peptide complexes and affect T-cell recognition.