Paula A. Guidry
University of Texas Southwestern Medical Center
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Featured researches published by Paula A. Guidry.
Human Molecular Genetics | 2010
David R. Karp; Nishanth Marthandan; Steven G. E. Marsh; Chul Ahn; Frank C. Arnett; David S. DeLuca; Alexander D. Diehl; Raymond Dunivin; Karen Eilbeck; Michael Feolo; Paula A. Guidry; Wolfgang Helmberg; Suzanna E. Lewis; Maureen D. Mayes; Christopher J. Mungall; Darren A. Natale; Bjoern Peters; Effie Petersdorf; John D. Reveille; Barry Smith; Glenys Thomson; Matthew Waller; Richard H. Scheuermann
We describe a novel approach to genetic association analyses with proteins sub-divided into biologically relevant smaller sequence features (SFs), and their variant types (VTs). SFVT analyses are particularly informative for study of highly polymorphic proteins such as the human leukocyte antigen (HLA), given the nature of its genetic variation: the high level of polymorphism, the pattern of amino acid variability, and that most HLA variation occurs at functionally important sites, as well as its known role in organ transplant rejection, autoimmune disease development and response to infection. Further, combinations of variable amino acid sites shared by several HLA alleles (shared epitopes) are most likely better descriptors of the actual causative genetic variants. In a cohort of systemic sclerosis patients/controls, SFVT analysis shows that a combination of SFs implicating specific amino acid residues in peptide binding pockets 4 and 7 of HLA-DRB1 explains much of the molecular determinant of risk.
Journal of Neuroimmunology | 2010
Ann J. Ligocki; L. Lovato; D. Xiang; Paula A. Guidry; Richard H. Scheuermann; S.N. Willis; Stefany Almendinger; Michael K. Racke; Elliot M. Frohman; David A. Hafler; Kevin C. O'Connor; Nancy L. Monson
B cells isolated from the CSF of patients with multiple sclerosis (MS) have a unique accumulation of somatic hypermutation within the B cell receptor, termed the antibody gene signature (AGS). The focus of this study was to investigate whether the AGS could also be detected in MS brain tissue. Genetic analysis of B cells isolated from post-mortem CNS tissue samples from four MS brains demonstrated that signature enriched B cells are present at the site of tissue injury as well as in the circulating CSF.
Journal of Immunology | 2005
Paula A. Guidry; Iwona Stroynowski
The gastrointestinal tract is populated by a multitude of specialized immune cells endowed with receptors for classical (class Ia) and nonclassical (class Ib) MHC proteins. To identify class I products that engage these receptors and impact immunity/tolerance, we studied gut-transcribed class Ib loci and their polymorphism in inbred, outbred, and wild-derived mice. Intestinal tissues enriched in epithelial cells contained abundant transcripts of ubiquitously expressed and preferentially gut-restricted Q and T class I loci. The latter category included the “blastocyst Mhc” gene, H2-Bl, and its putative paralog, Tw5. Expression of H2-Bl was previously detected only at the maternal/fetal interface, where it was proposed to induce immune tolerance via interactions with CD94/NKG2A receptors. Analysis of coding region polymorphism performed here revealed two major alleles of H2-Bl with conserved residues at positions critical for class I protein folding and peptide binding. Both divergent alleles are maintained in outbred and wild mice under selection for fecundity and pathogen resistance. Surprisingly, we found that alternative splicing of H2-Bl mRNA in gut tissues is prevalent and allele-specific. It leads to strain-dependent expression of diverse repertoires of canonical and noncanonical transcripts that may give rise to distinct ligands for intestinal NK cell, T cell, and/or intraepithelial lymphocyte receptors.
Immunogenetics | 2011
Nora E. Renthal; Paula A. Guidry; Sharmila Shanmuganad; William Renthal; Iwona Stroynowski
Although the human nonclassical class Ib major histocompatibility complex (Mhc) locus, HLA-G, is known to act as an immune suppressor in immune-privileged sites, little is currently known regarding participation of the rodent class Ib Mhc in similar pathways. Here, we investigated the expression properties of the mouse nonclassical Mhc H2-Q5k gene, previously detected in tumors and tissues associated with pregnancy. We find that H2-Q5k is alternatively spliced into multiple novel isoforms in a wide panel of C3H tissues. Unlike other known class I MHC, it is most highly transcribed in the brain, where the classical class Ia Mhc products are scarce. The truncated isoforms are selectively enriched in sites of immune privilege and are translated into cell surface proteins in neural crest-derived transfected cells. Furthermore, we present data supporting a model whereby Q5k isoforms serve an immune-protective role by donating their Qdm leader peptide to Qa-1, in a pathway homologous to the HLA-G leader fragment binding HLA-E and inhibiting CD94/NKG2A-positive cytotoxic cells. In addition, we report a previously unknown homolog of H2-Q5k in the C57BL/6 mouse, which encodes Qdm, but is transcribed solely into noncanonical isoforms. Collectively, these studies demonstrate that H2-Q5k, and its homologous class I-like H2b gene may play tissue-specific roles in regulating immune surveillance.
pacific symposium on biocomputing | 2010
Glenys Thomson; Nishanth Marthandan; Jill A. Hollenbach; Steven J. Mack; Henry A. Erlich; Richard M. Single; Matthew Waller; Steven G.E. Marsh; Paula A. Guidry; David R. Karp; Richard H. Scheuermann; Susan D. Thompson; David N. Glass; Wolfgang Helmberg
Human Immunology | 2011
Steven J. Mack; Paula A. Guidry; Nishanth Marthandan; Thomas Smith; John M. Campbell; Patrick Dunn; David R. Karp; Richard M. Single; Glenys Thomson; Jeffrey Wiser; Richard H. Scheuermann; Henry A. Erlich
Journal of Immunology | 2009
Nishanth Marthandan; David R. Karp; Frank C. Arnett; Matthew Waller; Paula A. Guidry; Michael Feolo; Steven G.E. Marsh; Richard H. Scheuermann
Journal of Immunology | 2012
Richard H. Scheuermann; Nishanth Marthandan; Paula A. Guidry; Glenys Thomson; Frank C. Arnett; David R. Karp
Journal of Immunology | 2011
Nishanth Marthandan; Paula A. Guidry; Glenys Thomson; Frank C. Arnett; David R. Karp; Richard H. Scheuermann
Journal of Immunology | 2011
Ann J. Ligocki; William Rounds; Lindsay G. Cowell; Parul Chaudhary; Diane Xiang; Paula A. Guidry; Richard H. Scheuermann; Michael K. Racke; Ardith Courtney; Elliot M. Frohman; Benjamin Greenberg; Nancy L. Monson