As long as this was possible, Jerne was a firm believer in the notion that antibodies are the sole molecular basis of immunological specificity and of idiotypic network interactions1,2. In defending this notion, he had to deal with recalcitrant implications derived from the genetic control of immune responsiveness, notably the growing evidence that essentially all Ir genes were found to map to the MHC. Since Ir genes controlled the responsiveness of T cells in an antigen-specific fashion, what was more plausible than to propose that the antigen receptors of T cells were the direct products of these Ir genes, and thus of genes linked to the MHC? These ideas were put forward by prominent immunologists including Hugh McDevitt and Baruj Benacerraf, both pioneers in studies of Ir genes3. Since antibody genes were definitely not linked to the MHC, notably Benacerraf and coworkers suggested that T cell antigen receptors, on cells and in secreted form, were different from immunoglobulins and represented another, second class of antigen-specific receptors in the immune system3, 4, 5. A fundamental difference between the receptors of T cells and antibodies was further supported by experiments showing that T cells recognized protein antigens differently from antibodies and B cells. Whereas B cells reacted to conformational epitopes that were destroyed by denaturing the protein, T cells reacted to sequential epitopes that were resistant to denaturation.
KeywordsCell Receptor Heavy Chain Gene Idiotypic Network Antibody Heavy Chain Cell Receptor Gene
Unable to display preview. Download preview PDF.
Chapter 10 References
- 1.Jerne NK (1974–1975) The immune system: a web of V-domains. Harvey Lect 70, Series 93–110Google Scholar
- 2.Jerne NK (1974) Towards a network theory of the immune system. Ann Immunol Inst Pasteur 125C: 373Google Scholar
- 5.Germain RN, Benacerraf B (1980) Helper and suppressor T cell factors. Springer Semin Immunopathol 93–127Google Scholar
- 10.Marchalonis JJ, Decker JM, DeLuca D, Moseley J M, Smith P, Warr G W (1977) Lymphocyte surface immunoglobulins, evolutionary origin and involvement in activation. Cold Spring Harb Symp Quant Biol 41: 261 Du Pasquier L, Weiss N, Loor F (1972) Direct evidence for immunoglobulins on the surface of thymus lymphocytes of amphibian larvae. Eur J Immunol 2: 366–370 Ruben LN, Van der Hoven A, Dutton RW (1973) Cellular cooperation in hapten-carrier responses in the newt, Triturus viridescens. Cell Immunol 6: 300–314 Emmrich F, Richter RF, Ambrosius H (1975) Immunoglobulin determinants on the surface of lymphoid cells of carps. Eur J Immunol 5: 76–78 Yocum D, Cuchens M, Clem LW (1975) The hapten-carrier effect in teleost fish. J Immunol 114: 925–927PubMedGoogle Scholar
- 15.Krawinkel U, Cramer M, Mage RG, Kelus AS, Rajewsky K (1977) Isolated hapten-binding receptors of sensitized lymphocytes. II. Receptors from nylon wool-enriched rabbit T lymphocytes lack serological determinants of immunoglobulin constant domains but carry the A locus allotypic markers. J Exp Med 146: 792–801PubMedCrossRefGoogle Scholar
- 16.Krawinkel U, Cramer M, Imanishi-Kari T, Jack RS, Rajewsky K, Makela O (1977) Isolated hapten-binding receptors of sensitized lymphocytes. I. Receptors from nylon wool-enriched mouse T lymphocytes lack serological markers of immunoglobulin constant domains but express heavy chain variable portions. Eur J Immunol 7: 566–573PubMedCrossRefGoogle Scholar
- 22.Adam G, Weiler E (1976) Lymphocyte population dynamics during ontogenic generation of diversity. In: Cunningham AJ (ed): The Generation of Antibody Diversity. Academic Press, New York, 1–20Google Scholar
- 23.Rajewsky K (1984) Mechanisms of idiotypic control of the antibody repertoire. In: Greene MI, Nisonoff A (eds): The Biology of Idiotypes. Plenum Press, New York, 477Google Scholar
- 32.Rothbard JB (1990) The ternary complex: T cell receptor, MHC protein, and immunogenic peptide. Semin Immunol 5: 283–295Google Scholar