Abstract
The helper T-cell response to globular proteins appears, in general, to require intracellular processing of the antigen, such that a peptide fragment containing the T-cell antigenic determinant is released and transported to and held on the surface of an Ia-expressing, antigen-presenting cell. However, the molecular details underlying these phenomena are largely unknown. The means by which antigenic peptides are anchored on the antigen-presenting cell surface was investigated. A cell surface protein is identified that was isolated by its ability to bind to a 24-amino acid peptide fragment of pigeon cytochrome c, residues 81-104, containing the major antigenic determinant for B10.A mouse T cells. This peptide binding protein, purified from [35S]methionine-labeled cells, appears as two discrete bands of approximately equal to 72 and 74 kDa after NaDodSO4/PAGE. The protein can be eluted from the peptide affinity column with equivalent concentrations of either the antigenic pigeon cytochrome c peptide or the corresponding nonantigenic peptide of mouse cytochrome c. However, it does not bind to the native cytochromes c, either of pigeon or mouse, and thus the protein appears to recognize some structure available only in the free peptides. This protein plays a role in antigen presentation as evidenced by the ability of rabbit antibodies raised against it to block the activation of an antigen-specific T-cell hybrid by antigen-presenting cells and pigeon cytochrome c. Its expression is not major histocompatibility complex-restricted in that the blocking activity of the antisera can be absorbed on spleen cells from mice of different haplotypes. This peptide binding protein can be isolated from a variety of cell types, including B cells, T cells, and fibroblasts. The anchoring of processed peptides on the cell surface by such a protein may play a role in antigen presentation--facilitating the interaction of antigenic peptides with Ia and/or the T-cell receptor.
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- Abbas A. K., Haber S., Rock K. L. Antigen presentation by hapten-specific B lymphocytes. II. Specificity and properties of antigen-presenting B lymphocytes, and function of immunoglobulin receptors. J Immunol. 1985 Sep;135(3):1661–1667. [PubMed] [Google Scholar]
- Austin P., Trowsdale J., Rudd C., Bodmer W., Feldmann M., Lamb J. Functional expression of HLA-DP genes transfected into mouse fibroblasts. Nature. 1985 Jan 3;313(5997):61–64. doi: 10.1038/313061a0. [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]
- Babbitt B. P., Matsueda G., Haber E., Unanue E. R., Allen P. M. Antigenic competition at the level of peptide-Ia binding. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4509–4513. doi: 10.1073/pnas.83.12.4509. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brautigan D. L., Ferguson-Miller S., Margoliash E. Mitochondrial cytochrome c: preparation and activity of native and chemically modified cytochromes c. Methods Enzymol. 1978;53:128–164. doi: 10.1016/s0076-6879(78)53021-8. [DOI] [PubMed] [Google Scholar]
- Buus S., Colon S., Smith C., Freed J. H., Miles C., Grey H. M. Interaction between a "processed" ovalbumin peptide and Ia molecules. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3968–3971. doi: 10.1073/pnas.83.11.3968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Casten L. A., Lakey E. K., Jelachich M. L., Margoliash E., Pierce S. K. Anti-immunoglobulin augments the B-cell antigen-presentation function independently of internalization of receptor-antigen complex. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5890–5894. doi: 10.1073/pnas.82.17.5890. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Corradin G., Harbury H. A. Cleavage of cytochrome c with cyanogen bromide. Biochim Biophys Acta. 1970 Dec 22;221(3):489–496. doi: 10.1016/0005-2795(70)90219-9. [DOI] [PubMed] [Google Scholar]
- Cresswell P. Intracellular class II HLA antigens are accessible to transferrin-neuraminidase conjugates internalized by receptor-mediated endocytosis. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8188–8192. doi: 10.1073/pnas.82.23.8188. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dickerson R. E., Takano T., Eisenberg D., Kallai O. B., Samson L., Cooper A., Margoliash E. Ferricytochrome c. I. General features of the horse and bonito proteins at 2.8 A resolution. J Biol Chem. 1971 Mar 10;246(5):1511–1535. [PubMed] [Google Scholar]
- Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
- Hannum C. H., Matis L. A., Schwartz R. H., Margoliash E. The B10.A mouse B cell response to pigeon cytochrome c is directed against the same area of the protein that is recognized by B10.A T cells in association with the Ek beta:Ek alpha Ia molecule. J Immunol. 1985 Nov;135(5):3314–3322. [PubMed] [Google Scholar]
- Jelachich M. L., Lakey E. K., Casten L., Pierce S. K. Antigen presentation is a function of all B cell subpopulations separated on the basis of size. Eur J Immunol. 1986 Apr;16(4):411–416. doi: 10.1002/eji.1830160417. [DOI] [PubMed] [Google Scholar]
- Kovac Z., Schwartz R. H. The molecular basis of the requirement for antigen processing of pigeon cytochrome c prior to T cell activation. J Immunol. 1985 May;134(5):3233–3240. [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lakey E. K., Margoliash E., Flouret G., Pierce S. K. Peptides related to the antigenic determinant block T cell recognition of the native protein as processed by antigen-presenting cells. Eur J Immunol. 1986 Jul;16(7):721–727. doi: 10.1002/eji.1830160702. [DOI] [PubMed] [Google Scholar]
- Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature. 1985 Apr 11;314(6011):537–539. doi: 10.1038/314537a0. [DOI] [PubMed] [Google Scholar]
- Malissen B., Price M. P., Goverman J. M., McMillan M., White J., Kappler J., Marrack P., Pierres A., Pierres M., Hood L. Gene transfer of H-2 class II genes: antigen presentation by mouse fibroblast and hamster B-cell lines. Cell. 1984 Feb;36(2):319–327. doi: 10.1016/0092-8674(84)90225-3. [DOI] [PubMed] [Google Scholar]
- Nairn R., Spengler M. L., Hoffman M. D., Solvay M. J., Thomas D. W. Macrophage processing of peptide antigens: identification of an antigenic complex. J Immunol. 1984 Dec;133(6):3225–3234. [PubMed] [Google Scholar]
- Phillips M. L., Yip C. C., Shevach E. M., Delovitch T. L. Photoaffinity labeling demonstrates binding between Ia molecules and nominal antigen on antigen-presenting cells. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5634–5638. doi: 10.1073/pnas.83.15.5634. [DOI] [PMC free article] [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]
- Streicher H. Z., Berkower I. J., Busch M., Gurd F. R., Berzofsky J. A. Antigen conformation determines processing requirements for T-cell activation. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6831–6835. doi: 10.1073/pnas.81.21.6831. [DOI] [PMC free article] [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]
- Turkewitz A. P., Sullivan C. P., Mescher M. F. Large-scale purification of murine I-Ak and I-Ek antigens and characterization of the purified proteins. Mol Immunol. 1983 Nov;20(11):1139–1147. doi: 10.1016/0161-5890(83)90137-2. [DOI] [PubMed] [Google Scholar]
- Ultee M. E., Margoliash E., Lipkowski A., Flouret G., Solinger A. M., Lebwohl D., Matis L. A., Chen C., Schwartz R. H. The T lymphocyte response to cytochrome c--II. Molecular characterization of a pigeon cytochrome c determinant recognized by proliferating T lymphocytes of the B10.A mouse. Mol Immunol. 1980 Jul;17(7):809–822. doi: 10.1016/0161-5890(80)90030-9. [DOI] [PubMed] [Google Scholar]
- Unanue E. R. Antigen-presenting function of the macrophage. Annu Rev Immunol. 1984;2:395–428. doi: 10.1146/annurev.iy.02.040184.002143. [DOI] [PubMed] [Google Scholar]
- Watts T. H., Gaub H. E., McConnell H. M. T-cell-mediated association of peptide antigen and major histocompatibility complex protein detected by energy transfer in an evanescent wave-field. Nature. 1986 Mar 13;320(6058):179–181. doi: 10.1038/320179a0. [DOI] [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]





