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P S Corser

Publications and source records attributed to P S Corser.

4 recordsLinked to original sources

Biochemical evidence for multiple I-E Ia molecules.

Sequential immunoprecipitation and isoelectric focusing analyses with monoclonal I-E-specific antibodies presented in this paper indicate the existence of multiple I-E molecules. In sequential immunoprecipitations with 13-4 (anti-Ia.7) and 17-3-3 (anti-Ia.22) monoclonal antibodies, 17-3-3 only partially cleared I-E molecules immunoprecipitated by 13-4. Similarly, 13-4 monoclonal antibody only partially cleared I-E molecules precipitated by 17-3-3 monoclonal antibody. These results suggested a minimum of three I-E molecules. One I-E molecule expresses both 13-4 and 17-3-3 determinants, a second I-E molecule expresses only 17-3-3 determinants, and a third I-E molecule expresses only 13-4 determinants. Isoelectric focusing analyses of I-E molecules immunoprecipitated by 13-4 and 17-3-3 showed differences in both Ae beta polypeptide chains and E alpha polypeptide chains. The sequential immunoprecipitation and isoelectric focusing analyses presented in this paper can be explained by a model in which there are at least two separate Ae genes being encoded within the I-A subregion and two separate E alpha genes being encoded within the I-E subregion. The 17-3-3 monoclonal antibody would recognize a determinant on only one of two Ae beta polypeptide chains and the 13-4 monoclonal antibody would recognize a determinant on only one of two E alpha polypeptide chains.

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

Ia specificity 22 is expressed on a hybrid I-E molecule formed by the association of a beta chain (Ae) coded for by the I-A subregion and an alpha chain (E alpha) encoded by the I-E subregion. Ia.22 can be generated by the complementation of Ab, Ak, As, Ar, with Ed, Ek, Ep, Er, Ew3, Eu, Ev but Eb, Ef, Eq, and Es. With the exception of H-2p which does not complement with As to generate Ia.22, all Ia. 7-positive (I-E) haplotypes can provide the permissive E alpha allele. It is postulated that Ia.22 is a combinatorial Ia determinant generated by the association of the alpha and beta chains. These determinants are probably involved in the immune recognition of antigens under dual Ir-gene control.

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Serologic and biochemical analyses of a variant Ae (E beta) ia polypeptide chain in D2.gD (H-2g2).

Recombinant D2.Gd (KdAdBbJbEbCbSbDb) was derived from parental strains B6 (H-2b) and DBA/2 H-2d). Recent peptide studies and 2-D electrophoresis studies from other laboratories have shown that the Aed (E beta) chain of D2.GD is structurally different from the parental-derived chain. An antiserum (D2.GD X A. TFR5)F1 anti-DBA/2 was produced that detects an Ia specificity (Ia.50) in the I-E molecule formed by the parent Aed chain and lacking in the I-E molecule formed by the variant Aed. chain. The variant Ae chain could have derived either from a mutational event or an intracistronic cross-over.

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Gene complementations to generate Ia antigens (Ia.23) on hybrid molecules.

Ia specificity 23 is a "combinatorial" antigen generated on a hybrid I region molecule, formed by the noncovalent binding of a 26,000- to 28,000-dalton beta polypeptide chain (Ae) coded by a gene in the I-A subregion with a 32,000- to 35,000-dalton alpha chain (E alpha) coded by a gene in the I-E subregion of the mouse H-2 gene complex. For expression of Ia.23, the Ae chain must be derived from the H-2d haplotype (I-Ad), while the E alpha can be provided by I-Ed, I-Ek, I-Ep, I-Er, I-Ev, and I-Ew3, but not I-Eb, I-Ef, I-Eq, I-Es, and I-Eu. With the exception of H-2u haplotype, all Ia.7 (I-E)-positive haplotypes can provide the permissive E alpha chain for generating Ia.23 by trans-complementation. In the H-2d haplotype, Ia.23 is generated by cis-complementation of Ad with Ed. Lymphocytes of F1 animals expressed two I-E subregion coded hybrid Ia specificities; one formed by cis-complementation and another by trans-complementation. It is postulated that such hybrid determinants are involved in the recognition and generation of immune response to antigens such as GL-Phe and cytochrome C where dual Ir gene control has been demonstrated. It is also suggested that there are two types of Ia specificities: (1) allotypic Ia specificities expressed on the alpha or beta chains (these could aid in the binding between the alpha and beta chains such as Ia.7); and (2) hybrid Ia specificities which are unique interaction determinants formed by the specific association of the alpha and beta chains (e.g., Ia.22,23). These interaction gene products may be involved in antigen recognition and presentation.

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