HLA‐D Region Molecules Restrict Proliferative T Cell Responses to Antigen

Thorsby, E.; Berle, E.; Nousiaonen, H.

doi:10.1111/j.1600-065x.1982.tb00433.x

Cited by 93 publications

(25 citation statements)

References 33 publications

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“…Comparison of the nucleotide sequence of the first domain of this second SB p-chain gene to that of SB p I, DR (3,and DC 3(10) shows unequivocally that this second SB p-chain gene belongs to the SB family. Consequently, we refer to this second SB gene as SB p II.…”

Section: Discussionmentioning

confidence: 99%

“…In the human MIJC (HLA), the proliferative and self-restrictive properties of class II molecules have been mapped to the D region of the HLA complex (2). The biochemical equivalent of HLA-D is thought to be the HLA-DR molecules (3), which are encoded in the DR subregion. A second group of polymorphic class II antigens, HLA-DC, is also encoded in the HLA-D region (4).…”

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confidence: 99%

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Molecular organization of the HLA-SB region of the human major histocompatibility complex and evidence for two SB beta-chain genes.

Gorski¹,

Rollini²,

Long³

et al. 1984

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

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The class II products of the major histocompatibility complex, also called Ia antigens, are composed of two polypeptide chains, the a and P chains, both encoded within the major histocompatibility complex. In man, the class II antigens can be divided into three biochemically distinct grodps called HLA-DR, HLA-DC, and HLA-SB. Our isolation of cDNA clones for the polymorphic fi chain of HLA-DR and HLA-DC has allowed us to study the organization of the class II genes. Here we identify the HLA-SB (-chain gene in recombinant clones from a cosmid library generated from a consanguineous homozygous B-cell line. The SB 3-chain gene is linked to the SB a-chain gene and the two genes are in opposite orientation. A second SB (&chain gene, corresponding to a new SB 3II locus, has also been identified and cloned. The SB 3chain genes show much less allelic restriction site polymorphism than the genes for the ( chains of HLA-DR or HLA-DC. MATERIALS AND METHODSConstruction of the Cosmid Library. Details of the cosmid library will be published elsewhere. In brief, DNA from the consanguineous homozygous cell line HHK was partially digested with Sau3A1 and fractionated on sucrose density gradients. DNA fractions of 35-40 kilobases (kb) were collected and ligated with arms of cosmid pOPF (12), which had been treated with phosphatase. The ligation mix was packaged in vitro (13) and introduced into Escherichia coli ED8767. The packaged cosmids were spread, replicated (14), and screened by colony filter hybridization (15). A DNA fragment from a DR p-chain genomic clone (unpublished data) labeled by nick-translation was used for these hybridizations. Colonies that were positive after three rounds of screening were grown and cosmid DNA was prepared.Identification of a Possible SB f3 cDNA Clone. The cloning of class II p-chain cDNA clones from a DR4,w6 cell line has been described (9 (Fig. 1) 3934The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Molecular organization of the HLA-SB region of the human major histocompatibility complex and evidence for two SB beta-chain genes.

Gorski¹,

Rollini²,

Long³

et al. 1984

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

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“…Although HLA-DR, -DQ, and -DP products can all present Ag to T cells (1), human Ag-specific T cell responses appear to be mainly DR restricted (2). It is unclear if this relates to functional differences between the different locus products or relates more to experimental artifacts in cloning procedures, for example DQ-restricted T cells may require growth factors not present in the culture medium or specific APC.…”

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confidence: 99%

Duplicated DQ Haplotypes Increase the Complexity of Restriction Element Usage in Cattle

Glass

Oliver

Russell

2000

The Journal of Immunology

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The MHC of cattle encodes two distinct isotypes of class II molecules, DR and DQ. Unlike humans, cattle lack the DP locus and about half the common haplotypes express duplicated DQ genes. The number and frequency of DQA and DQB alleles means that most cattle are heterozygous. If inter- and/or intrahaplotype pairing of DQA and DQB molecules occurs, cattle carrying DQ-duplicated haplotypes may express more restriction elements than would be predicted by the number of expressed alleles. We are investigating whether duplicated haplotypes cause differences in immune response, particularly in terms of generating protective immunity. We have analyzed the Ag-presenting function of DQ molecules in two heterozygous animals, one of which carries a duplicated haplotype. We compared the class II isotype specificity of T cell clones recognizing a putative vaccinal peptide from foot-and-mouth disease virus (FMDV15). We show for the first time that bovine T cells can recognize Ag in the context of DQ molecules. We also present evidence that interhaplotype pairings of DQA and DQB molecules form functional restriction elements. Both animals showed distinct biases to usage of particular restriction elements. Mainly DQ-restricted clones were derived from the animal with duplicated DQ genes, whereas the majority of clones from the animal with a single DQ gene pair were DR restricted. Furthermore, haplotype bias was observed with both animals. These experiments show that understanding of class II chain pairing in addition to knowledge of the genotype may be important in vaccine design where effective epitope selection is essential.

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“…Recognition of epitopes on nominal antigens, together with MHC determinants, is a necessary event for the activation of T lymphocytes. Several human diseases, most ofwhich are characterized by autoimmune phenomena, have been associated with HLA determinants, in particular with MHC class II (HLA-D) molecules (3)(4)(5). These MHC class II molecules function as restriction elements for T helper cells (6).…”

Section: Introductionmentioning

confidence: 99%

Shared T cell recognition sites on human histocompatibility leukocyte antigen class II molecules of patients with seropositive rheumatoid arthritis.

Goronzy¹,

Weyand²,

Fathman³

1986

J. Clin. Invest.

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HLA‐D Region Molecules Restrict Proliferative T Cell Responses to Antigen

Cited by 93 publications

References 33 publications

Molecular organization of the HLA-SB region of the human major histocompatibility complex and evidence for two SB beta-chain genes.

Molecular organization of the HLA-SB region of the human major histocompatibility complex and evidence for two SB beta-chain genes.

Duplicated DQ Haplotypes Increase the Complexity of Restriction Element Usage in Cattle

Shared T cell recognition sites on human histocompatibility leukocyte antigen class II molecules of patients with seropositive rheumatoid arthritis.

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