       Document 0985
 DOCN  M9620985
 TI    MHC class I expression and CD8+ T cell development in TAP1/beta
       2-microglobulin double mutant mice.
 DT    9602
 AU    Ljunggren HG; Van Kaer L; Sabatine MS; Auchincloss H Jr; Tonegawa S;
       Ploegh HL; Center for Cancer Research, Massachusetts Institute of;
       Technology, Cambridge 02139, USA.
 SO    Int Immunol. 1995 Jun;7(6):975-84. Unique Identifier : AIDSLINE
       MED/96082364
 AB    We have bred to homozygosity gene disruptions for the transporter
       associated with antigen processing 1 (TAP1) and beta 2-microglobulin
       (beta 2m), each of which plays a distinct role in providing class I MHC
       subunits. Surface expression of H-2Kb or Db on cells derived from
       TAP1/beta 2m -/- mice was undetectable by immunofluorescence or
       immunoprecipitation, unlike the situation observed for TAP1 -/- and beta
       2m -/- single mutant mice. Yet, TAP1/beta 2m -/- cells were able to
       elicit a CD8+ cytotoxic T cell (CTL) response in mice of different H-2
       haplotypes and could be killed by anti-H-2b specific CTL. Furthermore,
       TAP1/beta 2m /- skin grafts were rejected by bm1 mutant mice. This
       suggests that very low levels of conformed class I heavy chains can
       reach the cell surface even in the complete absence of TAP1 and beta 2m
       gene products, and that these molecules may select a functional CD8+ T
       cell repertoire. Indeed, CD4-CD8+ T cells were detected in TAP1/beta 2m
       -/- mice, but in numbers lower than in either of the single mutant mice.
       Nonetheless, it was possible to elicit a CD8+ allospecific and H-2b
       reactive CTL response in TAP1/beta 2m -/- mice. In line with this,
       TAP1/beta 2m -/- mice rapidly rejected TAP1/beta 2m +/- skin grafts. Our
       results suggest that some MHC class I heavy chains in TAP1/beta 2m -/-
       cells can reach the cell surface in a form that allows recognition by
       allospecific CTL and positive selection of CD8+ T cells.
 DE    beta 2-Microglobulin/*GENETICS/IMMUNOLOGY  Animal  ABC
       Transporters/*GENETICS/IMMUNOLOGY  Crosses, Genetic  CD8-Positive
       T-Lymphocytes/*IMMUNOLOGY  Epitopes/GENETICS  Female  Histocompatibility
       Antigens Class I/*GENETICS  Isoantigens/GENETICS  Lymphocyte
       Transformation/*GENETICS  Male  Mice  Mice, Inbred C57BL  Mice, Mutant
       Strains  Skin Transplantation  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

