Relative contribution of "determinant selection" and "holes in the T-cell repertoire" to T-cell responses

TY - JOUR

T1 - Relative contribution of "determinant selection" and "holes in the T-cell repertoire" to T-cell responses

AU - Schaeffer, E B

AU - Sette, A

AU - Johnson, D L

AU - Bekoff, M C

AU - Smith, J A

AU - Grey, H M

AU - Buus, S

N1 - Keywords: Animals; Cell Line; Epitopes; Histocompatibility Antigens Class II; Immunity, Cellular; Lymphoma; Major Histocompatibility Complex; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Mice, Inbred Strains; Micrococcal Nuclease; Peptides; T-Lymphocytes

PY - 1989

Y1 - 1989

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 2471972

SN - 0027-8424

VL - 86

SP - 4649

EP - 4653

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 12

ER -