Abundance of H-2 promiscuous T cells specific for mycobacterial determinants in H-2b/d F1 hybrid mice.
A majority of immunodominant epitopes of mycobacterial antigens are known to be recognized by murine T cells in the context of several H-2 haplotypes. In this study, we established the frequency of T cells able to recognize these peptides promiscuously, i.e. in the context of allogeneic antigen-presenting cells, using hybridomas from peptide-immunized H-2 homologous and heterologous mice. The degree of promiscuity in homozygous mice varied between 4-27% between different specificities and genetic backgrounds. In particular, the results showed that promiscuity between Ab and Ad in respect to a peptide from the Mycobacterium tuberculosis 38-kDa protein (residues 350-369) was displayed by 22% of BALB/c and 4% of C57BL/10-derived hybrids, but by 42% of [BALB/c x C57BL/10] F1-derived clones. This represents a significant increase (p < 0.001) of T cell promiscuity compared to the parental haplotypes. It is noteworthy that considerably lower peptide concentrations were able to stimulate the promiscuous hybridomas compared to the H-2-restricted hybrids. This finding suggests a functional advantage of promiscuous T cells which enables them to expand preferentially in the initial stages of infections with M. tuberculosis and thus enables the host to mount a rapid protective immune response.
Vordermeier
H M
HM
MRC Clinical Sciences Centre, Hammersmith Hospital, London, GB.
Arya
A
A
Harris
D P
DP
Moreno
C
C
Ivanyi
J
J
D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology*; D003433:Crosses, Genetic; D005260:Female; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000942:Antigens, Bacterial; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell