The orientation of a T cell receptor to its MHC class II:peptide ligands.
The TCR found on CD4 T cells recognizes peptides bound to self MHC class II molecules as well as non-self MHC class II molecules. We have used the receptor on a cloned T cell line called D10.G4.1 (D10) to perform a structure-function analysis of this interaction. The D10 T cell clone recognizes not only a peptide from conalbumin (CA-wt) bound to syngeneic I-Ak against which it was raised, but also the allogeneic MHC molecules I-A(b,v,p,q,d). In the present study, we show that residue 30 in complementarity-determining region 1 (CDR1) of the TCR alpha-chain interacts with the I-A alpha-chain at hvr2 (residues 52, 53, and 55). We also show that residue 51 in CDR2 of the TCR alpha-chain interacts with the peptide at peptide residue 2. Finally, we show that residue 29 in CDR1 of the TCR beta-chain affects recognition of the glutamic acid at residue 66 in the I-A beta-chain. These data suggest an orientation of TCR relative to its peptide:MHC class II ligands. We argue that this orientation will be shared by all CD4 TCRs, and that it is only subtly different from the common orientation proposed for receptors binding to MHC class I.
Hong
S C
SC
Section of Immunobiology, Yale University School of Medicine, and Howard Hughes Medical Institute, New Haven, CT 06520, USA.
Sant'Angelo
D B
DB
Dittel
B N
BN
Medzhitov
R
R
Yoon
S T
ST
Waterbury
P G
PG
Janeway
C A
CA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008024:Ligands; D051379:Mice; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000276:immunology*; D013329:Structure-Activity Relationship
D000949:Histocompatibility Antigens Class II; D008024:Ligands; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta