Abstract
Most mice display two conventional major histocompatibility complex class II isotypes, A and E. Several A+E- strains have been observed, but never any that are A-E+. Because of this and because of hints from several lines of functional analysis, it has been proposed that the two isotypes might not operate equivalently. This proposition has not been directly testable until now because of the lack of an E-only strain. We report the production of such mice, exploiting previously created class II-transgenic and class II-"knock-out" lines. A+E-, A-E-, and A-E+ littermates have been compared by a number of parameters. We find that E and A molecules are, for the most part, functionally equivalent. However, subtle differences are seen in their ability to engage CD4 molecules on immature thymocytes, and in the profile of receptors on T cells selected into the periphery.
Full Text
The Full Text of this article is available as a PDF (681.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allan W., Tabi Z., Cleary A., Doherty P. C. Cellular events in the lymph node and lung of mice with influenza. Consequences of depleting CD4+ T cells. J Immunol. 1990 May 15;144(10):3980–3986. [PubMed] [Google Scholar]
- Benoist C., Mathis D. Positive and negative selection of the T cell repertoire in MHC class II transgenic mice. Semin Immunol. 1989 Nov;1(2):117–124. [PubMed] [Google Scholar]
- Benoist C., Mathis D. Positive selection of the T cell repertoire: where and when does it occur? Cell. 1989 Sep 22;58(6):1027–1033. doi: 10.1016/0092-8674(89)90501-1. [DOI] [PubMed] [Google Scholar]
- Bill J., Kanagawa O., Linten J., Utsunomiya Y., Palmer E. Class I and class II MHC gene products differentially affect the fate of V beta 5 bearing thymocytes. J Mol Cell Immunol. 1990;4(5):269–280. [PubMed] [Google Scholar]
- Bill J., Kanagawa O., Woodland D. L., Palmer E. The MHC molecule I-E is necessary but not sufficient for the clonal deletion of V beta 11-bearing T cells. J Exp Med. 1989 Apr 1;169(4):1405–1419. doi: 10.1084/jem.169.4.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Candéias S., Katz J., Benoist C., Mathis D., Haskins K. Islet-specific T-cell clones from nonobese diabetic mice express heterogeneous T-cell receptors. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6167–6170. doi: 10.1073/pnas.88.14.6167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Candéias S., Waltzinger C., Benoist C., Mathis D. The V beta 17+ T cell repertoire: skewed J beta usage after thymic selection; dissimilar CDR3s in CD4+ versus CD8+ cells. J Exp Med. 1991 Nov 1;174(5):989–1000. doi: 10.1084/jem.174.5.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Corley R. B., LoCascio N. J., Ovnic M., Haughton G. Two separate functions of class II (Ia) molecules: T-cell stimulation and B-cell excitation. Proc Natl Acad Sci U S A. 1985 Jan;82(2):516–520. doi: 10.1073/pnas.82.2.516. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cosgrove D., Gray D., Dierich A., Kaufman J., Lemeur M., Benoist C., Mathis D. Mice lacking MHC class II molecules. Cell. 1991 Sep 6;66(5):1051–1066. doi: 10.1016/0092-8674(91)90448-8. [DOI] [PubMed] [Google Scholar]
- Jones P. P., Murphy D. B., McDevitt H. O. Variable synthesis and expression of E alpha and Ae (E beta) Ia polypeptide chains in mice of different H-2 haplotypes. Immunogenetics. 1981;12(3-4):321–337. doi: 10.1007/BF01561674. [DOI] [PubMed] [Google Scholar]
- Liao N. S., Maltzman J., Raulet D. H. Expression of the V beta 5.1 gene by murine peripheral T cells is controlled by MHC genes and skewed to the CD8+ subset. J Immunol. 1990 Feb 1;144(3):844–848. [PubMed] [Google Scholar]
- Lightman S., Cobbold S., Waldmann H., Askonas B. A. Do L3T4+ T cells act as effector cells in protection against influenza virus infection. Immunology. 1987 Sep;62(1):139–144. [PMC free article] [PubMed] [Google Scholar]
- MacDonald H. R., Lees R. K., Schneider R., Zinkernagel R. M., Hengartner H. Positive selection of CD4+ thymocytes controlled by MHC class II gene products. Nature. 1988 Dec 1;336(6198):471–473. doi: 10.1038/336471a0. [DOI] [PubMed] [Google Scholar]
- Marrack P., Kappler J. The staphylococcal enterotoxins and their relatives. Science. 1990 May 11;248(4956):705–711. doi: 10.1126/science.2185544. [DOI] [PubMed] [Google Scholar]
- Mengle-Gaw L., McDevitt H. O. Genetics and expression of mouse Ia antigens. Annu Rev Immunol. 1985;3:367–396. doi: 10.1146/annurev.iy.03.040185.002055. [DOI] [PubMed] [Google Scholar]
- Nakayama T., June C. H., Munitz T. I., Sheard M., McCarthy S. A., Sharrow S. O., Samelson L. E., Singer A. Inhibition of T cell receptor expression and function in immature CD4+CD8+ cells by CD4. Science. 1990 Sep 28;249(4976):1558–1561. doi: 10.1126/science.2120773. [DOI] [PubMed] [Google Scholar]
- Oliveira D. B. F protein and immune suppression genes. Immunol Suppl. 1989;2:26–32. [PubMed] [Google Scholar]
- Sachs D. H., Cone J. L., Humphrey G. W. The humoral response to an Ia antigen and skin graft rejection: mechanistic possibilities. Transplant Proc. 1976 Sep;8(3):413–416. [PubMed] [Google Scholar]
- Takahama Y., Ono S., Ishihara K., Muramatsu M., Hamaoka T. Disparate functions of I-A and I-E molecules on B cells as evidenced by the inhibition with anti-I-A and anti-I-E antibodies of polyclonal B cell activation. Eur J Immunol. 1989 Dec;19(12):2227–2235. doi: 10.1002/eji.1830191208. [DOI] [PubMed] [Google Scholar]
- Tomonari K., Lovering E. T-cell receptor-specific monoclonal antibodies against a V beta 11-positive mouse T-cell clone. Immunogenetics. 1988;28(6):445–451. doi: 10.1007/BF00355377. [DOI] [PubMed] [Google Scholar]
- Zuñiga-Pflücker J. C., McCarthy S. A., Weston M., Longo D. L., Singer A., Kruisbeek A. M. Role of CD4 in thymocyte selection and maturation. J Exp Med. 1989 Jun 1;169(6):2085–2096. doi: 10.1084/jem.169.6.2085. [DOI] [PMC free article] [PubMed] [Google Scholar]