The essence of epitopes.
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Amino Acid Sequence↗
Biomedical subjects
L D Barber
Publications and source records attributed to L D Barber.
HLA-B67: a member of the HLA-B16 family that expresses the ME1 epitope.
HLA-B67 is an uncommon antigen that has been defined by serological crossreactivity with the HLA-B7 and HLA-B16 (B38 and B39) antigens. It is found at highest frequency in certain Oriental populations and has been best defined in the Japanese. Nucleotide sequencing of cDNA encoding B67 reveals the B*6701 allele to be a subtype of B39 which differs from B*39011 by substitution at residues 67-71 of the alpha 1 helix. In the region of difference B*6701 is identical in sequence to B7, B22, B27 and related molecules that express the epitope recognized by the ME1 monoclonal antibody. That the HLA-B67 molecule binds strongly to the ME1 antibody was demonstrated by immunoprecipitation and cell surface binding assays. Identical B*6701 nucleotide sequences were obtained for the B67 alleles isolated from 2 unrelated Japanese and 1 North American caucasoid.
Alleles↗
The HLA-B73 antigen has a most unusual structure that defines a second lineage of HLA-B alleles.
The nucleotide sequence of cDNA encoding the HLA-B73 antigen was determined; it is unusually divergent, differing from other HLA-B alleles by 44-77 nucleotide substitutions. Features that distinguish the B*7301 heavy chain from other HLA-B heavy chains include multiple substitutions in the alpha 3 domain and a duplication-deletion within the transmembrane region that increases the length of B*7301 compared to other HLA-B heavy chains. The duplication-deletion is shared with subsets of B alleles from the homologous gorilla (Gogo-B) and chimpanzee (Patr-B) loci. Other unusual features of B*7301 are individually shared with certain alleles of the HLA-A, HLA-C, HLA-F, Gogo-B and Patr-B loci. The B*7301 molecules has sequence elements in common with members of the B7 crossreacting group in the alpha 1 domain and is shown to possess the ME1 epitope, which is held in common with the B7, B22, B27, B42 and B67 antigens. B*7301 has a unique cysteine at position 270 of the alpha 3 domain which appears accessible but probably does not form disulphide-bonded B*7301 dimers in cell membranes. B*7301 represents a newly discovered but ancient lineage of HLA-B alleles that appears poorly represented in the modern human population.
Alleles↗
Peptide binding to major histocompatibility complex molecules.
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Amino Acid Sequence↗
Interactions between the amino-terminal domains of MHC class II molecules have a profound effect on serologic and T cell recognition: an analysis using recombinant HLA-DR/H-2E molecules.
A series of transfected L cell lines were generated expressing the products of wild-type or recombinant HLA-DR1/H-2Ek beta-chain-encoding genes paired to DR alpha or E alpha. The recombinant genes were created by reciprocal exchange of the gene segments encoding the amino (NH2)-terminal and carboxy (COOH)-terminal halves of the beta 1 domain and the beta 2 domain. The majority of the serologic determinants, predicted from the genetic composition of the class II dimers, were expressed indicating that no gross conformational changes were induced by the creation of the interspecies recombinant molecules. Subtle conformational variation was detected by the anti-H-2Eb,k,s mAb Y17. Epitope expression was dependent on the presence of the E alpha-chain and NH2-terminal sequence from the beta 1 domain of H-2Ek. Substitution of DR1 sequence in either region led to loss of recognition by Y17. This pattern of reactivity maps the Y17 epitope either to the E alpha-chain or to an exposed sequence on the fourth strand of the beta sheet of the beta 1 domain. If the Y17 epitope is located on the E alpha-chain this raises the interesting possibility that the conformation of this chain, which is invariant by sequence, may vary according to the beta-chain with which it is coexpressed. The ability of the recombinant class II dimers to present Ag to the pigeon cytochrome c-specific, H-2Ek-restricted T cell hybridoma 2B4 was assessed. Transfected L cells expressing E beta k paired to E alpha or DR alpha presented Ag with equal efficiency, and the beta 2 domain of H-2Ek could be substituted with the equivalent region from DR1 without any loss of response. Wild-type DR1 failed to function as a restriction element, however, substitution of the COOH-terminal portion of the beta 1 domain with the equivalent sequence from H-2Ek was sufficient to produce a partial recovery of Ag recognition. Cells expressing a recombinant beta 1 domain comprising the COOH-terminal sequence from H-2Ek and the NH2-terminal sequence from DR1 presented Ag when paired to DR alpha but failed to do so when paired to E alpha. This indicates that a subtle conformational disturbance caused by mismatching of the NH2-terminal region of the beta-chain and the alpha-chain can have pronounced effects on T cell recognition.(ABSTRACT TRUNCATED AT 400 WORDS)
Amino Acid Sequence↗
Contribution of T-cell receptor-contacting and peptide-binding residues of the class II molecule HLA-DR4 Dw10 to serologic and antigen-specific T-cell recognition.
The relative contributions of putative T-cell receptor (TCR)-contacting and peptide-binding residues of a major histocompatibility complex (MHC) class II restriction element to serologic and antigen-specific T-cell recognition were investigated by site-specific mutagenesis. Amino acids 70 and 71 in the DR beta 1 domain of DR4 Dw10 are uniquely differnet from the other Dw subtypes of DR4. Residue 70 is predicted to be located at the membrane-distal surface of the class II molecule, where it may influence T-cell recognition by a direct interaction with a TCR. Residue 71 is predicted to form part of the antigen-binding groove where its influence on T-cell recognition may be mediated indirectly via an effect on peptide binding. Transfected murine L cells were produced expressing the products of DR4 Dw10B genes in which the codons for residues 70 and 71 had been mutated towards DR4 Dw14. Support for the predicted orientations of beta-chain residues 70 and 71 was lent by the observation that only residue 70 plays an important role in the formation of a serologic determinant. Mutation of this residue was sufficient to produce recovery of recognition by a human monoclonal antibody, NI, which has specificity for all the DR4 subtypes with the exception of DR4 Dw10. The human T-cell clone HA1.7, specific for influenza virus hemagglutinin (HA) peptide 307-319 and restricted by DR1 Dw1, exhibits degeneracy of MHC restriction on the DR4 Dw subtypes with the exception of DR4 Dw10.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Melanin concentrating hormone inhibits the release of alpha MSH from teleost pituitary glands.
A radioimmunoassay was developed for salmonid melanin concentrating hormone (MCH) and used to measure immunoreactive (ir)MCH in the hypothalamus and pituitary of trout (Salmo gairdneri) and eels, (Anguilla anguilla) maintained under different regimes of background color. In trout, 95% of the total irMCH was located in the pituitary gland. The amount of MCH in both pituitary and hypothalamus was increased when white-adapted trout were transferred to a black background. In eels, a similar change of background led to an accumulation of MCH in the pituitary but not in the hypothalamus. The results suggest that MCH is released from the neurohypophysis in association with physiological color change. Neurointermediate lobes of trout and eels released both ir alpha MSH and irMCH when they were cultured in vitro. The release of alpha MSH was significantly enhanced when endogenous MCH was immunoabsorbed by MCH antiserum added to the culture medium. The results indicate that MCH can induce pallor in fish not only by its peripheral effect on the melanophores but also by an inhibitory action on the release of alpha MSH from the pituitary.
Anguilla↗
Bilateral iris tumors in an immunosuppressed child.
A seven-year-old iatrogenically immunosuppressed girl developed simultaneous bilateral iris tumors associated with granulomatous iridocyclitis, splenomegaly, and an immunoblastic pleocytosis. Serologic studies suggested a current active Epstein-Barr virus infection. Tumor biopsy showed a polyclonal plasmacytoid lymphoproliferative process, establishing the diagnosis of posttransplant lymphoproliferative disorder. Low-dose local irradiation produced rapid and complete iris tumor regression with restoration of vision in both eyes. To our knowledge, this is the first report of ocular involvement in posttransplant lymphoproliferative disorder.
Child↗