Abstract
The amino acid sequence corresponding to residues 107-116 of hen egg-white lysozyme (HEL) has been identified as containing an immunodominant T-cell epitope recognized in association with the I-Ed molecule. The immunodominance of this epitope in HEL-primed H-2d mice was demonstrated by analysis of the T-cell proliferative response induced by synthetic peptides covering almost the entire HEL sequence. All the T-cell hybridomas from H-2d mice analyzed recognize the HEL sequence 107-116 in association with the I-Ed molecule. Correlating with the restriction of T-cell recognition, HEL-(105-120)-peptide binds to I-Ed but not to I-Ad molecules. Conservative or semiconservative substitutions at positions 113 (Asn----Lys), 114 (Arg----His), or 115 (Cys----Ala) abrogate the ability of HEL-(105-120) to activate T cells. Substitutions at residues 113 and 115 affect T-cell recognition but not the binding to I-Ed molecules, whereas, as shown by binding data and competition experiments, an Arg----His substitution at position 114 profoundly impairs the capacity of the peptide to interact with I-Ed molecules. In agreement with these results, [Lys113]HEL-(105-120)-peptide but not [His114]HEL-(105-120)-peptide was found to be immunogenic in H-2d mice. Thus, a single semiconservative substitution drastically reduces binding capacity and abolishes immunogenicity, suggesting that a strict correlation exists between binding of a peptide to Ia molecules and its immunogenicity.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Buus S., Sette A., Colon S. M., Jenis D. M., Grey H. M. Isolation and characterization of antigen-Ia complexes involved in T cell recognition. Cell. 1986 Dec 26;47(6):1071–1077. doi: 10.1016/0092-8674(86)90822-6. [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]
- Buus S., Sette A., Grey H. M. The interaction between protein-derived immunogenic peptides and Ia. Immunol Rev. 1987 Aug;98:115–141. doi: 10.1111/j.1600-065x.1987.tb00522.x. [DOI] [PubMed] [Google Scholar]
- Buus S., Werdelin O. Oligopeptide antigens of the angiotensin lineage compete for presentation by paraformaldehyde-treated accessory cells to T cells. J Immunol. 1986 Jan;136(2):459–465. [PubMed] [Google Scholar]
- Dembić Z., Haas W., Weiss S., McCubrey J., Kiefer H., von Boehmer H., Steinmetz M. Transfer of specificity by murine alpha and beta T-cell receptor genes. Nature. 1986 Mar 20;320(6059):232–238. doi: 10.1038/320232a0. [DOI] [PubMed] [Google Scholar]
- Grey H. M., Colon S. M., Chesnut R. W. Requirements for the processing of antigen by antigen-presenting B cells. II. Biochemical comparison of the fate of antigen in B cell tumors and macrophages. J Immunol. 1982 Dec;129(6):2389–2395. [PubMed] [Google Scholar]
- Hopp T. P., Woods K. R. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katz M. E., Maizels R. M., Wicker L., Miller A., Sercarz E. E. Immunological focusing by th mouse major histocompatibility complex: mouse strains confronted with distantly related lysozymes confine their attention to very few epitopes. Eur J Immunol. 1982 Jul;12(7):535–540. doi: 10.1002/eji.1830120702. [DOI] [PubMed] [Google Scholar]
- Margalit H., Spouge J. L., Cornette J. L., Cease K. B., Delisi C., Berzofsky J. A. Prediction of immunodominant helper T cell antigenic sites from the primary sequence. J Immunol. 1987 Apr 1;138(7):2213–2229. [PubMed] [Google Scholar]
- Merrifield R. B., Vizioli L. D., Boman H. G. Synthesis of the antibacterial peptide cecropin A (1-33). Biochemistry. 1982 Sep 28;21(20):5020–5031. doi: 10.1021/bi00263a028. [DOI] [PubMed] [Google Scholar]
- Rock K. L., Benacerraf B. Inhibition of antigen-specific T lymphocyte activation by structurally related Ir gene-controlled polymers. Evidence of specific competition for accessory cell antigen presentation. J Exp Med. 1983 May 1;157(5):1618–1634. doi: 10.1084/jem.157.5.1618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz R. H. Immune response (Ir) genes of the murine major histocompatibility complex. Adv Immunol. 1986;38:31–201. doi: 10.1016/s0065-2776(08)60006-1. [DOI] [PubMed] [Google Scholar]
- Sette A., Adorini L., Marubini E., Doria G. A microcomputer program for probit analysis of interleukin-2 (IL-2) titration data. J Immunol Methods. 1986 Feb 12;86(2):265–277. doi: 10.1016/0022-1759(86)90463-1. [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]
- Sette A., Colizzi V., Appella E., Doria G., Adorini L. Analysis of lysozyme-specific immune responses by synthetic peptides. I. Characterization of antibody and T cell-mediated responses to the N-terminal peptide of hen egg-white lysozyme. Eur J Immunol. 1986 Jan;16(1):1–6. doi: 10.1002/eji.1830160102. [DOI] [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]
- Van Beneden R. J., Watson D. K., Chen T. T., Lautenberger J. A., Papas T. S. Cellular myc (c-myc) in fish (rainbow trout): its relationship to other vertebrate myc genes and to the transforming genes of the MC29 family of viruses. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3698–3702. doi: 10.1073/pnas.83.11.3698. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yagüe J., White J., Coleclough C., Kappler J., Palmer E., Marrack P. The T cell receptor: the alpha and beta chains define idiotype, and antigen and MHC specificity. Cell. 1985 Aug;42(1):81–87. doi: 10.1016/s0092-8674(85)80103-3. [DOI] [PubMed] [Google Scholar]