Highly biased CDR3 usage in restricted sets of beta chain variable regions during viral superantigen 9 response.
Superantigens encoded by the mouse mammary tumor virus can stimulate a large proportion of T cells through interaction with germline-encoded regions of the T cell receptor beta chain like the hypervariable region 4 (HV4) loop. However, several lines of evidence suggest that somatically generated determinants in the CDR3 region might influence superantigen responses. We stimulated T cells from donors differing at the BV6S7 allele with vSAG9 to assess the nature and structure of the T cell receptor in amplified T cells and to evaluate the contribution of non-HV4 elements in vSAG recognition. This report demonstrates that vSAG9 stimulation caused the expansion of TCR BV6-expressing T cells, although to varying degrees depending on the BV6 subfamily. The BV6S7 subfamily was preferentially expanded in all donors, but in donors homozygous for the BV6S7*2 allele, a significant number of BV6S5 T cells were amplified and showed a highly biased beta chain junctional region (BJ) and CDR3 usage. As CDR3 regions are involved in major histocompatibility complex (MHC)-peptide interaction, such a selection is highly suggestive of an intimate MHC-TCR interaction and would imply that the topology of the MHC-vSAG-TCR complex is similar to the one occurring during conventional antigen recognition.
Ciurli
C
C
Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Canada.
Posnett
D N
DN
Sékaly
R P
RP
Denis
F
F
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018448:Models, Immunological; D008969:Molecular Sequence Data; D005810:Multigene Family; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018089:Superantigens / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
D000956:Antigens, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens