While still incomplete, the first data concerning the biochemistry of T cell receptor-ligand interactions in cell-free systems seem to have considerable predictive value regarding whether a T cell response is strong or weak or suppressive. This data will help considerably in elucidating the mechanisms behind T cell responsiveness. Also of great interest are the first structures of T cell receptor molecules and, particularly, TCR-ligand complexes. These appear to confirm earlier suggestions of a fixed orientation for TCR engagement with peptide/MHC and should form the basis for understanding higher oligomers, evidence for which has also just emerged. We conclude with an analysis of the highly diverse CDR3 loops found in all antigen receptor molecules and suggest that such regions form the core of both TCR and antibody specificity.

Multiple DNA and protein sequence alignments have been constructed for the human T-cell receptor cVS, [3, and y (TCRA/D, B, and G) variable (V) gene segments. The traditional classification into subfamilies was confirmed using a much larger pool of sequences. For each sequence, a name was derived which complies with the standard nomenclature. The traditional numbering of V gene segments in the order of their discovery was continued and changed when in conflict with names of other segments_ By discriminating between alleles at the same locus versus genes from different loci, we were able to reduce the number of more than 150 different TCRBV sequences in the database to a repertoire of only 47 functional TCRBV gene segments. An extension of this analysis to the over 1 O0 TCRAV sequences results in a predicted repertoire of 42 functional TCRAV gene segments. Our alignment revealed two residues that distinguish between the highly homologous V8 and Vo~ one at a site that in VH contacts the constant region, the other at the interface between immunoglobulin Vn and VL. This site may be responsible for restricted pairing between certain V8 and Vy chains. On the other hand, V[3 and V 7 appear to be related by the fact that their CDR2 length is increased by four residues as compared with that of VcV8 peptides.The alignment data reported in this paper have been submitted to the EMBL nucleotide sequence database and have been assigned the alignment number DS23485. The data are available by the EBI FTP server and file server

We have analysed 19 complementary DNA clones encoding the alpha-chain of the T-cell antigen receptor derived from thymic transcripts, and find that 15 of them contain partial or complete variable (V alpha) genes. Seven of these genes cross-hybridize to over 40 germline V alpha gene segments in Southern blot analyses. Of the 19 joining (J alpha) sequences examined, 18 seem to be encoded by distinct gene segments, hence the repertoire of J alpha gene segments is much larger than those of the immunoglobulin or T-cell receptor beta-chain gene families. We suggest that the variable domains of immunoglobulins and T-cell antigen receptors are similar in structure.