Relative contribution of "determinant selection" and "holes in the T-cell repertoire" to T-cell responses.
Using BALB/c and CBA/J mice, the I-region associated (Ia) binding capacity and T-cell immunogenicity of a panel of 14 overlapping peptides that span the entire sequence of the protein staphylococcal nuclease (Nase) was examined to evaluate major histocompatibility gene complex (MHC) control of T-cell responses. Ia binding and Ia-restricted T-cell immunogenicity could be determined for a total of 54 peptide-MHC combinations. Only 30% of the 54 instances examined involved detectable Ia binding, but they represented almost all (12 of 13) of the immune responses found. However, binding to Ia was not sufficient to ensure T-cell immunogenicity, since only 70% of the binding events were productive--i.e., were associated with an immune response. Thus, Ia molecules have the expected characteristics of a highly permissive capacity for antigen interaction that allows them to function as restriction elements for a large universe of antigens. On the other hand, since the Ia molecules cannot distinguish between self and non-self, not all antigen-Ia interactions would be permitted to elicit a T-cell response. It appears that both Ia binding ("determinant selection") and T-cell repertoire act in concert to define the immune response status of an individual toward any particular T-cell epitope.
Schaeffer
E B
EB
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Sette
A
A
Johnson
D L
DL
Bekoff
M C
MC
Smith
J A
JA
Grey
H M
HM
Buus
S
S
D000818:Animals; D002460:Cell Line; D000939:Epitopes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007111:Immunity, Cellular; D008223:Lymphoma; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D008836:Micrococcal Nuclease / Q000138:chemical synthesis / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D008836:Micrococcal Nuclease