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The Journal of Immunology, 2003, 171: 274-284.
Copyright © 2003 by The American Association of Immunologists

A Novel Instance of Class I Modification (cim) Affecting Two of Three Rat Class I RT1-A Molecules Within One MHC Haplotype1

Andrea L. González-Muñoz2,*, Anne-France Le Rolle2,*, Hélène Brun{dagger}, Hans J. Hedrich{ddagger}, Dirk Wedekind{ddagger}, Simon J. Powis§, Etienne Joly3,*,{dagger} and Geoffrey W. Butcher3,*

* Molecular Immunology Program, The Babraham Institute, Cambridge, United Kingdom; {dagger} IFR Claude de Préval, CHU Purpan, Toulouse, France; {ddagger} Institut für Versuchstierkunde und Zentrales Tierlabor der Medizinischen Hochschule, Hannover, Germany; and § School of Life Sciences, University of Dundee, Dundee, United Kingdom

MHC class I expression by rats of the RT1o, RT1d, and RT1m MHC haplotypes was investigated. Identical, functional cDNAs were obtained from RT1o and BDIX (RT1dv1) rats for three MHC class I molecules. RT1-A1o/d and -A2o/d are closely related in sequence to other cloned rat class Ia genes that have been shown to map to the RT1-A region, while RT1-A3° is highly homologous to a class I gene identified by sequencing an RT1-An genomic contig and is named A3n. Detailed analysis of the three molecules was undertaken using serology with mAbs, two-dimensional gel analysis of immunoprecipitates, and killing assays using cytotoxic T cells. Arguments are presented suggesting that A1° is the principal MHC class Ia (classical) restricting element of this haplotype. A2°, which is highly cross-reactive with A1°, and A3° probably play more minor or distinct roles in Ag presentation. Unexpectedly, cDNAs encoding exactly the same three molecules were cloned from rats of the RT1m haplotype, an MHC that until now was thought to possess unique class Ia genes. RT1m contains the TAP-B allele of the TAP transporter, and we present evidence that functional polymorphism in rat TAP has an even greater impact on the expression of RT1-A1° and -A2° than it does on RT1-Aa in the established case of class I modification (cim). Historically, this led to the misclassification of RT1m class Ia molecules as separate and distinct.







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