Abstract
T cells generally recognize foreign antigens as peptides associated with self-molecules encoded by genes of the major histocompatibility complex (MHC). However, T cells which are specific for non-peptidic haptens have been described, in particular in patients with contact sensitivity reactions to metals such as nickel (Ni). Previously, we isolated MHC class II-restricted Ni-specific T cell clones from patients with Ni allergy. The experiments reported here examine the molecular basis for the interaction between Ni and peptide-MHC complexes. We find that Ni alters a T cell response to a peptide and show that Ni interacts with this peptide to alter its antigenicity rather than its ability to bind to MHC molecules. These findings hold implications for a model of hapten recognition by T cells.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987 Oct 8;329(6139):512–518. doi: 10.1038/329512a0. [DOI] [PubMed] [Google Scholar]
- Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
- Burakoff S. J., Germain R. N., Benacerraf B. Cross-reactive lysis of trinitrophenyl (TNP)-derivatized H-2 incompatible target cells by cytolytic T lymphocytes generated against syngeneic TNP spleen cells. J Exp Med. 1976 Dec 1;144(6):1609–1620. doi: 10.1084/jem.144.6.1609. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buus S., Sette A., Colon S. M., Grey H. M. Autologous peptides constitutively occupy the antigen binding site on Ia. Science. 1988 Nov 18;242(4881):1045–1047. doi: 10.1126/science.3194755. [DOI] [PubMed] [Google Scholar]
- Buus S., Sette A., Colon S. M., Miles C., Grey H. M. The relation between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides. Science. 1987 Mar 13;235(4794):1353–1358. doi: 10.1126/science.2435001. [DOI] [PubMed] [Google Scholar]
- Ciavarra R., Forman J. Cell membrane antigens recognized by anti-viral and anti-trinitrophenyl cytotoxic T lymphocytes. Immunol Rev. 1981;58:73–94. doi: 10.1111/j.1600-065x.1981.tb00350.x. [DOI] [PubMed] [Google Scholar]
- Clayberger C., Dekruyff R. H., Aisenberg J., Cantor H. Hapten-reactive inducer T cells. I. Definition of two classes of hapten-specific inducer cells. J Exp Med. 1983 Jun 1;157(6):1906–1919. doi: 10.1084/jem.157.6.1906. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GURD F. R., WILCOX P. E. Complex formation between metallic cations and proteins, peptides and amino acids. Adv Protein Chem. 1956;11:311–427. doi: 10.1016/s0065-3233(08)60424-6. [DOI] [PubMed] [Google Scholar]
- Guttinger M., Caspers P., Takacs B., Trzeciak A., Gillessen D., Pink J. R., Sinigaglia F. Human T cells recognize polymorphic and non-polymorphic regions of the Plasmodium falciparum circumsporozoite protein. EMBO J. 1988 Aug;7(8):2555–2558. doi: 10.1002/j.1460-2075.1988.tb03104.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kilgus J., Jardetzky T., Gorga J. C., Trzeciak A., Gillessen D., Sinigaglia F. Analysis of the permissive association of a malaria T cell epitope with DR molecules. J Immunol. 1991 Jan 1;146(1):307–315. [PubMed] [Google Scholar]
- Kilgus J., Romagnoli P., Guttinger M., Stuber D., Adorini L., Sinigaglia F. Vaccine T-cell epitope selection by a peptide competition assay. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1629–1633. doi: 10.1073/pnas.86.5.1629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matzinger P., Bevan M. J. Hypothesis: why do so many lymphocytes respond to major histocompatibility antigens? Cell Immunol. 1977 Mar 1;29(1):1–5. doi: 10.1016/0008-8749(77)90269-6. [DOI] [PubMed] [Google Scholar]
- Panina-Bordignon P., Tan A., Termijtelen A., Demotz S., Corradin G., Lanzavecchia A. Universally immunogenic T cell epitopes: promiscuous binding to human MHC class II and promiscuous recognition by T cells. Eur J Immunol. 1989 Dec;19(12):2237–2242. doi: 10.1002/eji.1830191209. [DOI] [PubMed] [Google Scholar]
- Pohlit H., Haas W., von Boehmer H. Cytotoxic T cell responses to haptenated cells. I. Primary, secondary and long-term cultures. Eur J Immunol. 1979 Sep;9(9):681–690. doi: 10.1002/eji.1830090905. [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]
- Shearer G. M., Rehn T. G., Garbarino C. A. Cell-mediated lympholysis of trinitrophenyl-modified autologous lymphocytes. Effector cell specificity to modified cell surface components controlled by H-2K and H-2D serological regions of the murine major histocompatibility complex. J Exp Med. 1975 Jun 1;141(6):1348–1364. doi: 10.1084/jem.141.6.1348. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sinigaglia F., Scheidegger D., Garotta G., Scheper R., Pletscher M., Lanzavecchia A. Isolation and characterization of Ni-specific T cell clones from patients with Ni-contact dermatitis. J Immunol. 1985 Dec;135(6):3929–3932. [PubMed] [Google Scholar]
- Sinigaglia F., Takacs B., Jacot H., Matile H., Pink J. R., Crisanti A., Bujard H. Nonpolymorphic regions of p190, a protein of the Plasmodium falciparum erythrocytic stage, contain both T and B cell epitopes. J Immunol. 1988 May 15;140(10):3568–3572. [PubMed] [Google Scholar]
- Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]