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P Parham

Publications and source records attributed to P Parham.

At least 199 records · Page 11Linked to original sources
PubMed1992

Reptilian class I major histocompatibility complex genes reveal conserved elements in class I structure.

The polymerase chain reaction was used to isolate clones with class I major histocompatibility complex sequences from fish (carp), amphibian (axolotl), and two species of reptile (lizard and snake). The lizard and snake clones were used to isolate class I cDNA clones. All the sequences showed the expected evolutionary relatedness. The carp and axolotl clones and one lizard cDNA clone lacked the first cysteine in the alpha 3 domain which in other class I heavy chains forms an intradomain disulfide bond. A small number of amino acid residues are conserved in the class I heavy chain sequences from all five classes of vertebrates. In the first two domains they are symmetrically clustered and contribute to intra- and interdomain contacts. None of these invariant residues are at peptide-binding, T-cell receptor-interacting, or CD8-binding positions.

Amino Acid Sequence↗
PubMed1992

HLA class I nucleotide sequences, 1992.

The HLA class I sequences included in this compilation are taken from articles listed in the literature: "Nomenclature for Factors of the HLA System, 1991" [1], "Nomenclature for Factors of the HLA System, 1990" [2], and "Nomenclature for Factors of the HLA System, 1989" [3]. Because of the increased number of sequences, we have only included sequences for exons 2-4 in this compilation. Where discrepancies have arisen between reported sequences, the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list, and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments, identity between nucleotides is indicated by a hyphen (-). An unavailable sequence is indicated by a period (.). Gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number.

Base Sequence↗
PubMed1992

The molecular basis for reactivity of anti-Cw1 and anti-Cw3 alloantisera with HLA-B46 haplotypes.

HLA haplotypes containing the HLA-B46 allele react with both anti-Cw1 and anti-Cw3 alloantisera, a pattern of reactivity defined as the Cw11 antigen and postulated to involve either a distinctive Cw11 allele or a duplicated HLA-C locus. From serological characterization of CIR cells transfected with B46 cDNA we now demonstrate that the anti-Cw3 reactivity with these haplotypes is solely due to the B46 molecule and not to an HLA-C molecule. Furthermore, isolation and characterization of HLA-C mRNA from cells expressing B46 strongly suggest that anti-Cw1 reactions are directed against the product of a conventional Cw1 allele. The antigenic cross-reactivities of B46 with B62 and Cw3 correlate with its chimaeric primary structure, which is identical to that of B62, except in the alpha 1 helix where it is identical to both Cw3 and Cw1. The structure, distribution and genetic linkage of B46 indicate it is of recent, Asian origin and is the result of a gene conversion, involving Cw1 as the donor gene and B62 as the recipient. These results demonstrate that the Cw11 antigen neither corresponds to a novel HLA-C allele nor a duplicated HLA-C locus, but to a combination of epitopes contributed by linked Cw1 and B46 alleles. The nucleotide sequence we previously and erroneously attributed to a distinct Cw11 allele is now demonstrated to encode Cw8. Isolation of the cDNA clone with this sequence from a library made from a cell homozygous for the B46 haplotype was probably an artefact of contamination.

Alleles↗
PubMed1992

HLA class I nucleotide sequences, 1992.

The HLA Class I sequences included in this compilation are taken from publications listed in the papers: Nomenclature for factors of the HLA system, 1991 (1), Nomenclature for factors of the HLA system, 1990 (2), and Nomenclature for factors of the HLA system, 1989 (3). Due to the increased number of sequences, we have only included sequences for exons 2, 3 and 4 in this compilation. Where discrepancies have arisen between reported sequences, the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments, identity between nucleotides is indicated by a hyphen (-). An unavailable sequence is indicated by a period (.). Gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number.

Base Sequence↗
PubMed1992

HLA-B27 and disease: a consequence of inadvertent antigen presentation?

The close association of HLA-B27 with arthritic conditions has led to the suggestion that these diseases are mediated by cytotoxic T lymphocytes that recognize self-peptides presented by HLA-B27 molecules. The further association with enteric bacterial infections suggests that bacterial antigens may prime the CTL that later crossreacts on self. Bacterial infections do not usually generate CTL responses. We speculate here that unusual properties of HLA-B27 molecules may predispose to such responses. Thus, HLA-B27-related disease may be an unfortunate consequence of the generation of a suitable, self-mimicking HLA-B27-binding peptide by certain bacteria, plus an unusual propensity for the HLA-B27 molecule to bind and present such peptides.

Arthritis↗
PubMed1991

Gorilla class I major histocompatibility complex alleles: comparison to human and chimpanzee class I.

14 gorilla class I major histocompatibility complex (MHC) alleles have been isolated, sequenced, and compared to their counterparts in humans and chimpanzees. Gorilla homologues of HLA-A, -B, and -C were readily identified, and four Gogo-A, four Gogo-B, and five Gogo-C alleles were defined. In addition, an unusual Gogo class I gene with features in common with HLA-A and its related pseudogene, HLA-H, is described. None of the gorilla alleles is identical or even closely related to known class I alleles and each encodes a unique antigen recognition site. However, the majority of polymorphic substitutions and sequence motifs of gorilla class I alleles are shared with the human or chimpanzee systems. In particular, elements shared with HLA-A2 and HLA-B27 are found in Gogo-A and -B alleles. Diversity at the Gogo-B locus is less than at the Gogo-A locus, a trend the opposite of that seen for HLA-A and -B. The Gogo-C locus also appears to have limited polymorphism compared to Gogo-A. Two basic Gogo-C motifs were found and they segregate with distinctive sets of HLA-C alleles. HLA-A allels are divided into five families derived from two ancient lineages. All chimpanzee A alleles derived from one of these lineages and all gorilla alleles derive from the other. Unlike chimpanzee Patr-A alleles, the Gogo-A alleles do not clearly partition with one of the HLA-A families but have similarities with two. Overall, gorilla class I diversity appears from this sampling to show more distinctions from class I HLA than found for chimpanzee class I.

Alleles↗
PubMed1991

Molecular definition of a polymorphic antigen (LA45) of free HLA-A and -B heavy chains found on the surfaces of activated B and T cells.

A monomoprhic monoclonal antibody (LA45 antibody) reactive with "a new activation-induced surface structure on human T lymphocytes" (LA45 antigen) that resembled free class I heavy chains has recently been described (Schnabl, E., H. Stockinger, O. Majdic, H. Gaugitsch, I.J.D. Lindley, D. Maurer, A. Hajek-Rosenmayr, and W. Knapp. 1990. J. Exp. Med. 171:1431). This antibody was used to clone a class I-like heavy chain (LA45 gene) from the HUT 102 tumor cell, which paradoxically did not give rise to the LA45 antigen on transfection into monkey COS cells. We show here that the LA45 gene is HLA-Aw66.2, a previously uncharacterized allele of the HLA-A locus. The previously determined LA45 sequence differs from that of HLA-Aw66.2, from HUT 102, and the CR-B B cell line derived from the same individual as HUT 102 by substitution of tryptophan for serine at position 4 in the alpha 1 domain. Transfection of HLA-Aw66.2, and of a mutant of this gene with serine 4 substituted for tryptophan, into a human B cell line (C1R) both resulted in expression of the LA45 epitope. Furthermore, we find expression of the LA45 epitope on Epstein Barr virus-transformed B cell lines as well as lectin-activated T cells, but not on long-term T cell lines or unstimulated peripheral blood T cells. The specificity of the LA45 antibody is polymorphic and the presence of the LA45 epitope is precisely correlated with the sequence arginine, asparagine (RN) at residues 62 and 63 of the helix of the alpha 1 domain. The LA45 epitope is broadly distributed, being associated with half the alleles of both HLA-A and -B loci but none of the HLA-C locus. All the results are consistent with the presence of pools of free HLA-A and -B heavy chains at the surfaces of certain cell types but not others. Such molecules are probably responsible for the HLA-associated class I alloantigens of lectin-activated T cells. We hypothesize the free heavy chains result from dissociation of beta 2-microglobulin from subpopulations of empty HLA-A,B molecules, or molecules with weakly bound peptides, that vary in size depending on cellular activation and peptide supply.

Alleles↗
PubMed1991

Heterozygosity at individual amino acid sites: extremely high levels for HLA-A and -B genes.

The amino acid heterozygosities per site for HLA-A and -B loci are determined to be extremely high by combining population serotypic frequencies with amino acid sequences. For the 54 amino acid sites thought to have functional importance, the average heterozygosity per site is 0.301. Sixteen positions have heterozygosities greater than 0.5 at one or both loci and the frequencies of amino acids at a given position are very even, resulting in nearly the maximum heterozygosity possible. Furthermore, the high heterozygosity is concentrated in the peptide-interacting sites, whereas the sites that interact with the T-cell receptor have lower heterozygosity. Overall, these results indicate the importance of some form of balancing selection operating at HLA loci, maybe even at the individual amino acid level.

Alleles↗