Reconstitution of Ir Genes, Ia Antigens, and Mixed Lymphocyte Reaction Determinants by Gene Complementation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1981 Mar 1

PMID 6165020

Citations 25

Authors

C G Fathman

M Kimoto

R Melvold

C S David

Affiliations

Soon will be listed here.

Abstract

By using clones of murine T cells reactive with alloantigens as well as soluble antigens, it has been possible to demonstrate that Ia antigens, Ir gene phenomena (defined as the ability of immune T cells to recognize antigen), and mixed lymphocyte reaction (MLR)-stimulating determinants encoded within the I-A subregion are different manifestations associated with same product. These studies utilized the I-Ab mutant mouse B6.C-H-2bm (bm12), whose defect in the normal expression of the cell surface products of the I-Ab subregion can be partially circumvented through trans-complementation by deriving hybrids between bm12 and mice expressing normal I-A subregion products. Such mice [e.g., (bm12 X B10.A)F1] express several serologically normal I-Ab products but have defects in certain I-A subregion gene products normally expressed on cells of H-2a X H-2b heterozygote mice that are used as restricting elements for antigen recognition by antigen-reactive T cell clones or recognized as alloantigens by alloreactive T cell clones. This defect in cell surface expression of certain normal I-Ab products on the mutant bm12 cells has allowed us to suggest that there exist trans-complementing products on H-2a X H-2b heterozygote mice consisting of Ab alpha Ak beta and Ak alpha Ab beta that restrict antigen recognition by cloned T cells, stimulate MLR responses by cloned T cells, and react with certain anti-Ia antisera.

Citing Articles

Gain/loss of poly(Glu50Tyr50)/poly(Glu60Ala30Tyr10) responsiveness in the bm12 mutant strain.

Lei H, Melvold R, Miller S, Waltenbaugh C J Exp Med. 1982; 156(2):596-609.

PMID: 7047670 PMC: 2186774. DOI: 10.1084/jem.156.2.596.

Selective loss of antigen-specific Ir gene function in IA mutant B6.C-H-2bm12 is an antigen presenting cell defect.

Lin C, Rosenthal A, Passmore H, Hansen T Proc Natl Acad Sci U S A. 1981; 78(10):6406-10.

PMID: 7031650 PMC: 349048. DOI: 10.1073/pnas.78.10.6406.

Cell-mediated cytotoxicity to non-MHC alloantigens on mouse epidermal cells. VI. Influence of the MHC on the tissue specificity of cytotoxic T-lymphocyte responses.

TYLER J, Burlingham W, David C, Steinmuller D Immunogenetics. 1982; 16(1):23-36.

PMID: 6981598 DOI: 10.1007/BF00364439.

Murine T cell-specific Ia antigens: monoclonal antibodies define an I-A-encoded T lymphocyte structure.

Hayes C, Hullett D Proc Natl Acad Sci U S A. 1982; 79(11):3594-8.

PMID: 6980412 PMC: 346469. DOI: 10.1073/pnas.79.11.3594.

Tryptic peptide comparison of Ia antigen alpha and beta polypeptides from the I-A mutant B6.C-H-2bm12 and its congenic parental strain B6.

McKean D, Melvold R, David C Immunogenetics. 1981; 14(1-2):41-51.

PMID: 6948771 DOI: 10.1007/BF00344298.

References

Schwartz R, Yano A, Stimpfling J, Paul W . Gene complementation in the T-lymphocyte proliferative response to poly (Glu55Lys36Phe9)n. A demonstration that both immune response gene products must be expressed in the same antigen-presenting cell. J Exp Med. 1979; 149(1):40-57. PMC: 2184747. DOI: 10.1084/jem.149.1.40. View

Jones P, Murphy D, McDevitt H . Two-gene control of the expression of a murine Ia antigen. J Exp Med. 1978; 148(4):925-39. PMC: 2185029. DOI: 10.1084/jem.148.4.925. View

Fathman C, Hengartner H . Crossreactive mixed lymphocyte reaction determinants recognized by cloned alloreactive T cells. Proc Natl Acad Sci U S A. 1979; 76(11):5863-6. PMC: 411752. DOI: 10.1073/pnas.76.11.5863. View

Lafuse W, McCormick J, David C . Serological and biochemical identification of hybrid Ia antigens. J Exp Med. 1980; 151(3):709-15. PMC: 2185812. DOI: 10.1084/jem.151.3.709. View

Hansen T, Melvold R, Arn J, Sachs D . Evidence for mutation in an I-A gene. Nature. 1980; 285(5763):340-1. DOI: 10.1038/285340a0. View

Silver J, Swain S, Hubert J . Small subunit of I-A subregion antigens determines the allospecificity recognized by a monoclonal antibody. Nature. 1980; 286(5770):272-4. DOI: 10.1038/286272a0. View

Hengartner H, Fathman C . Clones of alloreactive T cells. I. A. unique homozygous MLR-stimulating determinant present on B6 stimulators. Immunogenetics. 1980; 10(2):175-84. DOI: 10.1007/BF01561566. View

Lerner E, Matis L, Janeway Jr C, Jones P, Schwartz R, Murphy D . Monoclonal antibody against an Ir gene product?. J Exp Med. 1980; 152(4):1085-101. PMC: 2185961. DOI: 10.1084/jem.152.4.1085. View

Kimoto M, Fathman C . Antigen-reactive T cell clones. I. Transcomplementing hybrid I-A-region gene products function effectively in antigen presentation. J Exp Med. 1980; 152(4):759-70. PMC: 2185955. DOI: 10.1084/jem.152.4.759. View

10.

McKenzie I, Sandrin M, Morgan G, Henning M, Melvold R . Mutation in the IA subregion of the murine H-2 complex. Immunogenetics. 1980; 11(1):103-6. DOI: 10.1007/BF01567775. View

11.

Frelinger J, Neiderhuber J, David C, Shreffler D . Evidence for the expression of Ia (H-2-associated) antigens on thymus-derived lymphocytes. J Exp Med. 1974; 140(5):1273-84. PMC: 2139718. DOI: 10.1084/jem.140.5.1273. View

12.

Schwartz R, David C, Sachs D, Paul W . T lymphocyte-enriched murine peritoneal exudate cells. III. Inhibition of antigen-induced T lymphocyte Proliferation with anti-Ia antisera. J Immunol. 1976; 117(2):531-40. View

13.

Klein J, Hauptfeld V . Ia antigens: their serology, molecular relationships, and their role in allograft reactions. Transplant Rev. 1976; 30:83-100. View

14.

Benacerraf B, Germain R . The immune response genes of the major histocompatibility complex. Immunol Rev. 1978; 38:70-119. DOI: 10.1111/j.1600-065x.1978.tb00385.x. View

15.

Schwartz R, David C, Dorf M, Benacerraf B, Paul W . Inhibition of dual Ir gene-controlled T-lymphocyte proliferative response to poly (Glu56Lys35Phe9)n with anti-Ia antisera directed against products of either I-A or I-C subregion. Proc Natl Acad Sci U S A. 1978; 75(5):2387-91. PMC: 392558. DOI: 10.1073/pnas.75.5.2387. View

16.

McKenzie I, Morgan G, Sandrin M, Michaelides M, Melvold R, Kohn H . B6.C-H-2bm12. A new H-2 mutation in the I region in the mouse. J Exp Med. 1979; 150(6):1323-38. PMC: 2185725. DOI: 10.1084/jem.150.6.1323. View