Unrestricted recognition of class I neodeterminants generated by exon shuffling

Horstmann, Ulrike; Arnold, Bernd; Hämmerling, Günter J.

doi:10.1002/eji.1830160725

Cited by 6 publications

(4 citation statements)

References 16 publications

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“…This molecule contains the signal sequence and the a1 domain of H-2Kd origin but the rest of the molecule is of Kk origin. The C31 antigen can stimulate T cells in an allogeneic manner, most likely due to neodeterminants (Horstmann et al, 1986). However, T cells specific for influenza A virus and restricted 3423 to recognize either Kd and Kk antigens do not recognize the C31 antigen.…”

Section: Introductionmentioning

confidence: 99%

Cytolytic T cells recognize a chimeric MHC class I antigen expressed in influenza A infected transgenic mice.

et al. 1988

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A chimeric H‐2Kd/Kk gene, called pC31, contains the extracellular alpha 1 domain of Kd origin whereas the rest of the molecule is of Kk origin. Disruption of the syngeneic alpha 1‐alpha 2 structure results in a total abrogation of the function of the C31 protein as a restriction element for H‐2Kd and Kk restricted T cells during virus infection. In an attempt to obtain information on the functional polymorphism of MHC class I antigens as restriction elements, we have introduced the pC31 gene into the germ line of C3H/He mice (H‐2k). The pC31 gene was transcribed in all tissues examined and the expression pattern paralleled the endogenous H‐2Kk gene. However, the mRNA for the transgene was approximately 10‐times more abundant, which was reflected in an elevated expression of the C31 protein in transgenic splenocytes. Most of the C31 antigen was found intracellularly. The C31 antigen could condition transgenic cytotoxic T lymphocytes in a specific manner during influenza A virus infection and functioned as the restricting element during T cell lysis of the infected cells. These results suggest that entire exons may be exchanged between MHC class I genes and that this exchange can generate novel and functional restriction elements.

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Section: Introductionmentioning

confidence: 99%

Cytolytic T cells recognize a chimeric MHC class I antigen expressed in influenza A infected transgenic mice.

et al. 1988

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“…However, we can not rule out the direct effect on oligomerization and/or transport . We should note here that the 20,000-30,000 molecules of C31 that we can detect at the cell surface by saturated binding assay seem to be normal, as evidenced by their higher molecular weight form, their insensitivity to Endo H after cell surface radio-iodination, and their demonstrated function in CTL assays (29,38) .…”

Section: Resultsmentioning

confidence: 72%

“…An antibody (1A2) against tubulin was used as a negative control to exclude the possibility that the iodine penetrated and labeled internal proteins (lanes 2 and 9) and OVA, which is Endo H sensitive, was used as a control for the efficiency of the enzymatic digestion (data not shown) . Therefore, the C31 expressed at the cell surface is properly processed, and the 20,000-30,000 molecules expressed at the surface of splenocytes account for the functional C31 molecules (29,38) .…”

Section: Resultsmentioning

confidence: 99%

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E3/19K from adenovirus 2 is an immunosubversive protein that binds to a structural motif regulating the intracellular transport of major histocompatibility complex class I proteins.

Jefferies

Burgert

1990

The Journal of Experimental Medicine

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SummaryWe have previously expressed in transgenic mice a chimeric H-2Kd/Kk protein called C31, which contains the extracellular a1 domain of Kd, whereas the rest of the molecule is of Kk origin. This molecule functions as a restriction element for alloreactive and influenza A-specific cytotoxic T lymphocytes (CTL) but is only weakly expressed at the cell surface of splenocytes. Here, we show that the low cell surface expression is the result ofslow intracellular transport and processing of the C31 protein . A set of hybrid molecules between Kd and Kk were used to localize the regions in major histocompatibility complex (MHC) molecules that are important for their intracellular transport and to further localize the structures responsible for binding to the adenovirus 2 E3/19K protein . This protein appears to be an important mediator of adenovirus persistence . It acts by binding to the immaturely glycosylated forms ofMHC class I proteins in the endoplasmic reticulum (ER), preventing their passage to the cell surface and thereby reducing the recognition ofinfected cells by virus-specific T cells . We find the surprising result that intracellular transport and E3/19K binding are controlled primarily by the first half of the second domain of Kd, thus localizing these phenomena to the five polymorphic residues in this region of the Kd protein. This result implies that the E3/19K protein may act by inhibiting peptide binding or by disrupting the oligomerization ofMHC class I molecules required for transport out ofthe ER. Alternatively, the E3/19K protein may inhibit the function of a positively acting transport molecule necessary for cell surface expression of MHC class I molecules .

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The ?1 and ?2 domains of H-2 class I molecules interact to form unique epitopes

et al. 1987

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Mouse class I antigens are the major targets of cytolytic T lymphocytes in both major histocompatibility complex (MHC)-restricted and allogeneic responses. Considerable evidence has recently accumulated demonstrating that MHC class I molecules encoded by genes whose alpha 1 and alpha 2 coding exons were interchanged are not recognized by T lymphocytes specific for parental class I products. Along with the loss of T-cell reactivity, there is a loss of recognition by some, but not all monoclonal antibodies. In this communication we report that the loss of reactivity by monoclonal antibodies is accompanied by the gain of new epitopes caused by the interaction of alpha 1 and alpha 2 domains. These epitopes are immunodominant. They are the major determinant recognized by polyclonal antisera raised by immunization with L cells transfected with exon-shuffled class I genes. Four new monoclonal antibodies have been produced which recognize at least two separate epitopes caused by the interaction of the alpha 1p and alpha 2d domains.

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Unrestricted recognition of class I neodeterminants generated by exon shuffling

Cited by 6 publications

References 16 publications

Cytolytic T cells recognize a chimeric MHC class I antigen expressed in influenza A infected transgenic mice.

Cytolytic T cells recognize a chimeric MHC class I antigen expressed in influenza A infected transgenic mice.

E3/19K from adenovirus 2 is an immunosubversive protein that binds to a structural motif regulating the intracellular transport of major histocompatibility complex class I proteins.

The ?1 and ?2 domains of H-2 class I molecules interact to form unique epitopes

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