An MHC interaction site maps to the amino-terminal half of the T cell receptor alpha chain variable domain.
We have used cloned T cell receptor (TCR) genes from closely related CD4 T cell lines to probe the interaction of the TCR with several specific major histocompatibility complex (MHC) class II ligands. Complementarity determining region 3 (CDR3) equivalents of both alpha and beta TCR chains are required for antigen-MHC recognition. Our data provide novel information about the rotational orientation of TCR-MHC contacts in that exchange of the amino terminal portion of the TCR alpha chain containing the putative CDR1 and CDR2 regions results in both gain and loss of MHC class II specificity by the resulting receptor. These two TCRs differ primarily in recognition of polymorphisms in the second hypervariable region of the MHC class II alpha chain. These results document the involvement of CDR1 and/or CDR2 of the TCR alpha chain in MHC recognition and suggest a rotational orientation of this TCR to its MHC ligand.
Hong
S C
SC
Section of Immunobiology, Howard Hughes Medical Institute, Yale University Medical School, New Haven, Connecticut 06510.
Chelouche
A
A
Lin
R H
RH
Shaywitz
D
D
Braunstein
N S
NS
Glimcher
L
L
Janeway
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002999:Clone Cells; D003207:Conalbumin / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000941:Antigens; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003207:Conalbumin