T cells with dual antigen specificity in T cell receptor transgenic mice rejecting allografts.
Allelic exclusion of T cell receptor (TCR) genes is incomplete: a significant percentage (10-30%) of normal human and mouse peripheral T cells express two surface TCR alpha chains, and a small percentage of peripheral human T cells have been reported to express two surface TCR beta chains. A proportion of thymocytes in TCR transgenic mice rearrange endogenous T cell receptor genes, and peripheral T cells with two TCR alpha chains, transgenic and endogenous, have been reported. T cell clones with more than a single TCR heterodimer on their surface might be expected to show specificity for more than one cognate antigen: we report here a T cell clone with dual antigen specificity, isolated from an F5 TCR influenza nucleoprotein (NP 366-374/Db)-specific transgenic female mouse which had rejected an H-2-matched male skin graft. It was selected in vitro by stimulation with male H-2b spleen cells in the absence of the NP366-374 peptide but has specificity for both H-Y/Db and NP366-374. This contrasted with the single NP366-374/Db specificity shown by a control clone isolated from a Rag1-/- F5 mouse. The dual antigen specificity was associated with the rearrangement of endogenous TCR genes and cell surface expression of these as well as the TCR transgene.
Simpson
E
E
Transplantation Biology Group, MRC Clinical Sciences Centre, RPMS, Hammersmith Hospital, London, GB.
Chandler
P
P
Sponaas
A
A
Millrain
M
M
Dyson
P J
PJ
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D001483:Base Sequence; D005260:Female; D005434:Flow Cytometry; D015329:Gene Rearrangement, T-Lymphocyte; D006084:Graft Rejection / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology; D006182:H-Y Antigen / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016038:Skin Transplantation / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000956:Antigens, Viral; D006183:H-2 Antigens; D006182:H-Y Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta