TY - JOUR
T1 - Substitutions in the HLA-DRα chain differentially affect DR7-restricted T-cell recognition of rabies virus antigen
AU - Fu, Xin Ting
AU - Saibara, Toshiji
AU - Karr, Robert W.
AU - Celis, Esteban
N1 - Funding Information:
We are grateful to Peter Gregersen for providing the DRB 1*040 1 cDNA, Sanna Goyert and Keith Guy for providing the monoclonal antibodies, and Jerry Brown and Larry Stern for providing the DRl structural coordinates. This work was supported by National Institutes of Health Grant A127214.
PY - 1996/2
Y1 - 1996/2
N2 - To investigate the functional roles of DRα residues in T-cell recognition, 20 mutants of the DRα chain were constructed by site-directed mutagenesis. These DRα mutants were expressed with WT DR(β1*0701) on mouse L cells and used as APC for four DR7-restricted T-cell clones specific for rabies virus antigens. The results indicate that the DRα residues are differentially involved in recognition of rabies virus antigen by different T-cell clones. Mutations in the floor of the antigen-binding groove (positions 9, 11, 22, and 24), on the α-helix (47, 55, 65, 66, and 72), and surprisingly on the outer loop (15, 18, and 19), abrogated recognition by at least one T-cell clone. Most of these residues appear to be involved in either peptide or TCR contact, based on the DR1 crystal structure. The involvement in T-cell recognition of DRα residues located in the outer loop outside the binding groove suggests that these residues may directly contact TCR, or indirectly contribute to the conformation of peptide sitting in the groove.
AB - To investigate the functional roles of DRα residues in T-cell recognition, 20 mutants of the DRα chain were constructed by site-directed mutagenesis. These DRα mutants were expressed with WT DR(β1*0701) on mouse L cells and used as APC for four DR7-restricted T-cell clones specific for rabies virus antigens. The results indicate that the DRα residues are differentially involved in recognition of rabies virus antigen by different T-cell clones. Mutations in the floor of the antigen-binding groove (positions 9, 11, 22, and 24), on the α-helix (47, 55, 65, 66, and 72), and surprisingly on the outer loop (15, 18, and 19), abrogated recognition by at least one T-cell clone. Most of these residues appear to be involved in either peptide or TCR contact, based on the DR1 crystal structure. The involvement in T-cell recognition of DRα residues located in the outer loop outside the binding groove suggests that these residues may directly contact TCR, or indirectly contribute to the conformation of peptide sitting in the groove.
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U2 - 10.1016/0198-8859(95)00155-7
DO - 10.1016/0198-8859(95)00155-7
M3 - Article
C2 - 8882408
AN - SCOPUS:0029944605
SN - 0198-8859
VL - 45
SP - 111
EP - 116
JO - Human Immunology
JF - Human Immunology
IS - 2
ER -