Identification of two cis-encoded HLA-DQ molecules that carry distinct alloantigenic specificities.

Johnson, Judith P.; Wank, Rudolf

doi:10.1084/jem.160.5.1350

Cited by 13 publications

(2 citation statements)

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“…A DQ-like antigen (33.1) has been reported whose expression is limited to B cells (Marti et al 1984); comparison of 33.1 sequences obtained by limited radiochemical sequencing with the sequences of DXa and DX^ suggest that the 33.1 antigen is not coded for by these genes. The presence of 2 DQ-like products in B LCLs has been reported (Karr et al 1984, Johnson & Wank 1984.…”

Section: The Dq(dc) Regionmentioning

confidence: 86%

Genetic Complexity and Expression of Human Class II Histocompatibility Antigens

Korman

Boss

Spies

et al. 1985

Immunological Reviews

238

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The genes encoding nearly all of the serologically defined class II antigens of the major histocompatibility complex have been isolated. Three class II loci have been studied in great detail. The DR region contains a single alpha gene and 3 beta chain genes, 1 of which is a pseudogene. The DR alpha chain gene has been linked to a DR beta gene which encodes a beta protein which contains the serological determinant MT3. A second cosmid cluster contains 2 beta genes, 1 of which encodes the DR4 allospecificity. The identification of these genes has been made by the comparison of amino terminal sequences of DR molecules obtained from a DR4 cell line and the deduced protein sequences of the beta 1 exons from cosmid and phage clones. A conserved element including the promoter and signal sequence is found at the 5' end of each of the 3 DR beta genes. Additionally, this element occurs three more times in the DR region, raising the question of whether additional beta chain genes might be found. The DQ region contains 2 pairs of genes, 1 of which encodes the DQ antigen. The 2nd pair of genes, called DX alpha and beta, appears to be capable of expressing a DQ-related product, although, to date, there is no evidence for its expression. The DP region also contains 2 pairs of genes. One pair encodes the DP antigen while the 2nd alpha-beta pair is shown to be composed of pseudogenes. The location of polymorphic regions in these genes and aspects of their relationship to the serology, evolution, and function of the class II MHC are discussed. The control of expression of class II genes by gamma-interferon has been examined. The promoters of class II genes are characterized by two conserved sequences common to all alpha and beta chain genes as well as by conserved sequences specific for either alpha or beta chain genes. In addition to studies of expression by DNA-mediated gene transformation, a system for the gene transfer of MHC antigens utilizing transmissible retrovirus vectors is described. Retrovirus vectors have been used to transmit DR alpha, DR beta, and the invariant chain (gamma) sequences to recipient cells with resultant expression of these proteins.

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Section: The Dq(dc) Regionmentioning

confidence: 86%

Genetic Complexity and Expression of Human Class II Histocompatibility Antigens

Korman

Boss

Spies

et al. 1985

Immunological Reviews

238

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“…with the Genox 3.53 epitope [18]. 16.23 is associated with the alloantigens DR3 and a subset of DRw6 and defines an epitope on a D R ( 3 chain [19].…”

Section: Classification Of Class I1 Molecules Defined By Mabmentioning

confidence: 99%

T cells specific for different antigens express different HLA‐D region products

Schendel

Johnson

1985

Eur J Immunol

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T cell lines and clones were analyzed for surface expression of Ia antigens using monoclonal antibodies (mAb) that detect monomorphic and polymorphic epitopes on Ia molecules encoded by the HLA-DR and HLA-DQ gene clusters. All mAb bound to B lymphocytes or lymphoblastoid cell lines of the same individuals from whom the T cells were derived. Three mAb detecting monomorphic epitopes, primarily associated with HLA-DR, bound to all T cells showing that each clone or line expressed some type of Ia. Three other mAb defining polymorphic epitopes associated with HLA-DR products showed differential binding patterns. Two reagents, R3 and E15/4 recognizing the supertypic specificity DRw52 (formerly MT2), bound to every alloreactive clone, whereas the 16.23 mAb, detecting a private DR3-associated epitope, failed to bind to any clone. In contrast, the 16.23 epitope was detected on high percentages of T cells specific for purified protein derivative of tuberculin (PPD) or tetanus toxoid (TT). Biochemical studies showed that the 16.23 and DRw52-like epitopes can be present on distinct DR molecules on B cell lines and this may also be the case for T cells. Three other mAb, detecting epitopes associated with HLA-DQ, also revealed differential binding patterns when tested on various T cells. Two failed to bind to any alloreactive clone and to only low numbers of PPD- or TT-specific T cell lines, whereas the third bound distinctly to a CD4+/CD8+ alloreactive clone. Biochemical analyses have shown that these DQ epitopes can be present on different molecules. Combined, these observations indicate that differential expression of Ia molecules encoded by both HLA-DR and DQ occurs between B and activated T cells as well as among T cell populations of the same individual. Whether these differences reflect quantitative variations in expression of given DR or DQ molecules or, alternatively, are due to differential class II gene expression in activated T cells remains to be determined.

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