Hybrid (combinatorial) Ia specificities: Gene complementations to generate Ia.22

Lafuse, William P.; McCormick, John; Corser, Paula S.; David, Chella S.

doi:10.1007/bf00524609

Cited by 7 publications

(2 citation statements)

References 26 publications

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“…Considerable serological evidence for the existence of unique antigenic determinants on certain A~:E~ complex has emerged recently. Four distinct determinants of this type have been defined: Ia.m44 recognized by the Y-17 (13) and 17-3-3 (29) monoclonal antibodies, Ia.m47 defined by the A303 monoclonal antibody developed by Harris and Delovitch (39), and Ia.22 and Ia.23 recognized by standard alloantisera (40,41). It is clear that T cells are also able to recognize unique combinatorial or conformational determinants (13,(42)(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

Immune response gene function correlates with the expression of an Ia antigen. I. Preferential association of certain Ae and E alpha chains results in a quantitative deficiency in expression of an Ae:E alpha complex.

McNicholas¹,

Murphy²,

Matis³

et al. 1982

The Journal of Experimental Medicine

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These studies were stimulated by the observation, reported in the accompanying paper (19), that IEu failed to interact with I-Ak or I-As in F1 mice to allow a response to the antigen, pigeon cytochrome c, unlike I-E subregions derived from other Ia.7+ haplotypes. Serological and biochemical analyses were performed to determine whether or not cells from these F1 mice express the Ak,se:E alpha complexes that should function as restriction elements for T cell recognition of pigeon cytochrome c on antigen-presenting cells. Using the Y-17 monoclonal antibody, which recognizes the combinatorial or conformational determinant Ia.m44 on certain Ae:E alpha complexes, we were able to distinguish between Aue:Eu alpha and Ab,k,se:Eu alpha complexes on cell surfaces. Although complement-dependent microcytotoxicity with Y-17 failed to detect Ab,k,se:Eu alpha complexes on cells from appropriate F1 mice, these molecules were detected by both quantitative absorption and quantitative immunofluorescence studies. However, Ab,k,se:Eu alpha complexes were found to be present at levels only one-seventh to one-eighth the levels expressed by homozygous I-Ab, I-Ek; I-Ak, I-Ek; and I-As, I-Ek cells. The results of two-dimensional polyacrylamide gel electrophoresis analyses suggest that the low levels of expression of Ab,k,se:Eu alpha complexes are a consequence of the preferential association of Aue and Eu alpha chains with each other in the F1 cells. As will be shown in the following paper (19), the quantitative deficiency in the expression of Ake:Eu alpha and Ase:Eu alpha complexes results in a corresponding defect in antigen-presenting cell function, thus providing strong evidence that Ia antigens represent products of Ir genes.

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Section: Discussionmentioning

confidence: 99%

Immune response gene function correlates with the expression of an Ia antigen. I. Preferential association of certain Ae and E alpha chains results in a quantitative deficiency in expression of an Ae:E alpha complex.

McNicholas¹,

Murphy²,

Matis³

et al. 1982

The Journal of Experimental Medicine

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“…Indeed, polymorphisms of individual proteins in multimeric molecules are seen in H-2 (j3-2 microglobulin and H-2) (25,26), immunoglobulin (heavy and light chains) (27,28), and Ly-2/3 (29). Combinatorial polymorphisms have also been described for H-2 (30), Qa-2 (31), and Ia (32), but at present it is not clear whether the Ly-15.2 epitope is chain specific or combinatorial. Most anti-LFA-1 monoclonal antibodies detect epitopes present on the a chain and it will be important to determine the chain location of the Ly-15.2 epitope, as one major advantage of alloantibodies is their use in gene mapping studies.…”

mentioning

confidence: 99%

The Ly-15 alloantigenic system: a genetically determined polymorphism of the murine lymphocyte function-associated antigen-1 molecule.

Hogarth

Walker

McKenzie

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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Serological and biochemical studies using monoclonal antibodies have demonstrated that the Ly-15 cell membrane alloantigens are polymorphic sites on the lymphocyte function-associated antigen-i (LFA-1) molecule. Ly-15.2 and LFA-1 show identical tissue distributions, being present on all thymocytes, lymphocytes, and neutrophils, and flow cytofluorometric analysis indicated identical cell surface expression of these molecules. Identity of Antibodies have been used to define several immunologically important cell membrane structures on effector T lymphocytes in mice. These are (i) the T-cell receptor complex (i.e., antigen receptor and associated molecules including T3 in man and its putative equivalent in mouse) (1, 2), (ii) the Ly-2/3 molecule (3, 4), (iii) L3T4 (5), and (iv) lymphocyte function-associated antigen-1 (LFA-1) (6-8). The importance of these cell membrane molecules in T-cell function is seen from experiments in which specific antibodies binding to these molecules enhance or inhibit a particular function (1-8). The precise mechanism of enhancement or inhibition is not fully understood, but in the case of LFA-1, LFA-1 antibodies inhibit T-cell killing by preventing effector/target cell conjugation (7,8). Thus, it is believed that the LFA-1 molecule acts by assisting in the stable attachment of the cytotoxic T cell to its target. Biochemical studies of the murine LFA-1 molecule have shown it to be a heterodimer composed of a Mr 180,000 a chain non-covalently associated with a M, 95,000 , chain (9). Furthermore, other studies have demonstrated that the LFA-1 molecule is related to the Mac-1 molecule, which is present only on granulocytes and macrophages and is the C3bi receptor (10). Mac-1 is a heterodimer of Mr 177,000 a chain non-covalently bound to the same Mr 95,000 13 chain that is part of the LFA-1 complex; therefore, LFA-1 and Mac-1 comprise a family of immunologically important molecules (8,11).Many genes encoding cell-membrane alloantigens have been described in the mouse and include the major histocompatibility complex, immunoglobulin genes, and the Ly loci. At present, there are 30 known Ly loci, which are defined by antibodies recognizing polymorphic forms of cell-membrane alloantigens (12,13) A Sepharose (Pharmacia) and labeled with Na125I, using chloramine-T.Binding assays were conducted in 96-well microtiter plates by mixing cells (5 x 105) suspended in phosphate-buffered saline containing 0.5% bovine serum albumin with 125I-labeled Ly-15.2 antibody (12.5-50 ,ug) in a total reaction volume of 100 ,l. Suspensions were incubated for 30 min at 4°C and washed repeatedly in phosphate-buffered saline containing bovine serum albumin. Plates were dried, and the radioactivity of individual wells was determined in a radiation counter.Cells. Thymus, lymph node, spleen, and bone marrow cells were prepared in phosphate-buffered saline containing bovine serum albumin. Ig-lymph node T cells were prepared by rosetting Ig+ B cells with sheep anti-mouse Ig-coatAbbreviation: LFA, lymphocyte functio...

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Ia Genes, Gene Products, and Determinants

David

Lafuse

1983

Ir Genes

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Hybrid (combinatorial) Ia specificities: Gene complementations to generate Ia.22

Cited by 7 publications

References 26 publications

Immune response gene function correlates with the expression of an Ia antigen. I. Preferential association of certain Ae and E alpha chains results in a quantitative deficiency in expression of an Ae:E alpha complex.

Immune response gene function correlates with the expression of an Ia antigen. I. Preferential association of certain Ae and E alpha chains results in a quantitative deficiency in expression of an Ae:E alpha complex.

The Ly-15 alloantigenic system: a genetically determined polymorphism of the murine lymphocyte function-associated antigen-1 molecule.

Ia Genes, Gene Products, and Determinants

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