Abstract
Nase-specific T cell recognize the 86-100 peptide in association with B10.A APC. Clone N40 recognizes the 86-100 peptide in association with B10.A (Ek alpha Ek beta) and B10.A (5R) (Ek alpha Eb beta) APCs. We demonstrate here that a single amino acid substitution in the staphylococcal nuclease protein alters the structure of the processed peptide such that the T cell epitope recognized by clone N40 was only available for recognition in conjunction with B10.A (5R) but not the B10.A APCs. Other Nase-specific T cells recognize the mutant nuclease, and a synthetic peptide corresponding to the immunodominant region of the mutant protein was stimulatory for all the Nase-specific T cells. These results suggest that the mutation either affects the processing of the protein into antigenic peptides or affects the conformation of the processed fragment differently from that of the peptide.
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Selected References
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- Adorini L., Appella E., Doria G., Nagy Z. A. Mechanisms influencing the immunodominance of T cell determinants. J Exp Med. 1988 Dec 1;168(6):2091–2104. doi: 10.1084/jem.168.6.2091. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Allen P. M., Matsueda G. R., Evans R. J., Dunbar J. B., Jr, Marshall G. R., Unanue E. R. Identification of the T-cell and Ia contact residues of a T-cell antigenic epitope. 1987 Jun 25-Jul 1Nature. 327(6124):713–715. doi: 10.1038/327713a0. [DOI] [PubMed] [Google Scholar]
- Babbitt B. P., Allen P. M., Matsueda G., Haber E., Unanue E. R. Binding of immunogenic peptides to Ia histocompatibility molecules. 1985 Sep 26-Oct 2Nature. 317(6035):359–361. doi: 10.1038/317359a0. [DOI] [PubMed] [Google Scholar]
- Bhayani H., Carbone F. R., Paterson Y. The activation of pigeon cytochrome c-specific T cell hybridomas by antigenic peptides is influenced by non-native sequences at the amino terminus of the determinant. J Immunol. 1988 Jul 15;141(2):377–382. [PubMed] [Google Scholar]
- Bodmer H. C., Gotch F. M., McMichael A. J. Class I cross-restricted T cells reveal low responder allele due to processing of viral antigen. Nature. 1989 Feb 16;337(6208):653–655. doi: 10.1038/337653a0. [DOI] [PubMed] [Google Scholar]
- Brett S. J., Cease K. B., Berzofsky J. A. Influences of antigen processing on the expression of the T cell repertoire. Evidence for MHC-specific hindering structures on the products of processing. J Exp Med. 1988 Jul 1;168(1):357–373. doi: 10.1084/jem.168.1.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carbone F. R., Moore M. W., Sheil J. M., Bevan M. J. Induction of cytotoxic T lymphocytes by primary in vitro stimulation with peptides. J Exp Med. 1988 Jun 1;167(6):1767–1779. doi: 10.1084/jem.167.6.1767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finnegan A., Smith M. A., Smith J. A., Berzofsky J., Sachs D. H., Hodes R. J. The T cell repertoire for recognition of a phylogenetically distant protein antigen. Peptide specificity and MHC restriction of staphylococcal nuclease-specific T cell clones. J Exp Med. 1986 Sep 1;164(3):897–910. doi: 10.1084/jem.164.3.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mengle-Gaw L., McDevitt H. O. Isolation and characterization of a cDNA clone for the murine I-E beta polypeptide chain. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7621–7625. doi: 10.1073/pnas.80.24.7621. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reddehase M. J., Rothbard J. B., Koszinowski U. H. A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes. Nature. 1989 Feb 16;337(6208):651–653. doi: 10.1038/337651a0. [DOI] [PubMed] [Google Scholar]
- Schwartz R. H. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol. 1985;3:237–261. doi: 10.1146/annurev.iy.03.040185.001321. [DOI] [PubMed] [Google Scholar]
- Sette A., Buus S., Colon S., Smith J. A., Miles C., Grey H. M. Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells. 1987 Jul 30-Aug 5Nature. 328(6129):395–399. doi: 10.1038/328395a0. [DOI] [PubMed] [Google Scholar]
- Shastri N., Miller A., Sercarz E. E. Amino acid residues distinct from the determinant region can profoundly affect activation of T cell clones by related antigens. J Immunol. 1986 Jan;136(2):371–376. [PubMed] [Google Scholar]
- Shimonkevitz R., Kappler J., Marrack P., Grey H. Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing. J Exp Med. 1983 Aug 1;158(2):303–316. doi: 10.1084/jem.158.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Widera G., Flavell R. A. The nucleotide sequence of the murine I-E beta b immune response gene: evidence for gene conversion events in class II genes of the major histocompatibility complex. EMBO J. 1984 Jun;3(6):1221–1225. doi: 10.1002/j.1460-2075.1984.tb01956.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ziegler H. K., Unanue E. R. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. Proc Natl Acad Sci U S A. 1982 Jan;79(1):175–178. doi: 10.1073/pnas.79.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
