Fine specificity and MHC restriction of trinitrophenyl-specific CTL.
In this study, the fine specificity and MHC restriction of a CTL response specific to the trinitrophenyl (TNP) hapten was analyzed. Based on the structure of peptide/Kb complexes and ternary TCR/Ag/MHC complexes, four TNP peptides, two octamers, and two nonamers were chosen for eliciting anti-TNP CTL responses. Hapten was conjugated at position 4 in the octamers and at position 5 in the nonamers, positions which should allow engagement of the hapten by TCRs. Potent CTL activity for each of the TNP peptides was obtained that was highly hapten-specific; however, there were considerable differences in the extent of cross-reactivity with other TNP peptides, with the octamers generating more cross-reactive CTL than the nonamers. MHC restriction analysis suggested that anti-hapten responses were less dependent on MHC recognition than anti-peptide responses. This was evidenced by the relative ease of detecting cross-reactivity to haptenated peptides presented by allo-MHC and by the relative insensitivity of anti-hapten vs anti-peptide CTL to mutations in the Kb molecule at potential TCR interaction sites. One potential explanation for this insensitivity to MHC mutation was the finding that the anti-hapten response appeared to be of higher avidity, since a > 100-fold difference in the amount of Ag required to sensitize target cells was found between these two types of Ags.
Franco
A
A
La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Yokoyama
T
T
Huynh
D
D
Thomson
C
C
Nathenson
S G
SG
Grey
H M
HM
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D002999:Clone Cells / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006241:Haptens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D009154:Mutation / Q000276:immunology; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014162:Transfection / Q000276:immunology; D014301:Trinitrobenzenes / Q000737:chemistry / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D006241:Haptens; D009842:Oligopeptides; D011948:Receptors, Antigen, T-Cell; D014301:Trinitrobenzenes