TY - JOUR
T1 - Alloreactive natural killer cells in the rat
T2 - complex genetics of major histocompabitility complex control
AU - Naper, Christian
AU - Vaage, John Torgils
AU - Lambracht, Doris
AU - Løvik, Guro
AU - Butcher, Geoffrey W.
AU - Wonigeit, Kurt
AU - Rolstad, Bent
PY - 1995/5
Y1 - 1995/5
N2 - A major role for the nonclassical major histocompatibility complex (MHC) class I region, i.e. RTI.C, in controlling rat natural killer (NK) cell alloreactivity has recently been established, and several findings suggested the existence of NK‐triggering alloantigens coded for by this region. Here, we have extended our studies on the MHC control of NK cell cytotoxicity against concanavalin A‐activated T cell blasts by comparing semi‐syngeneic and fully allogeneic combinations, and we show the following: (a) The self MHC exerted a strong influence on the NK allorecognition repertoire. (b) When anti‐F1 hybrid cytolytic activities of parental strain NK cells were measured, both recessively and non‐recessively inherited susceptibility patterns emerged. (c) In most combinations parental strain cells were lysed by F1 hybrid NK cells, thus resembling the hybrid resistance phenomenon described in mice. The cytotoxicity was lower in strain combinations where NK susceptibility was inherited non‐recessively, i.e. when parent anti‐F1 reactivity was detected, than in recessive combinations. (d) LEW.1LM1 (RT11m1) target cells, with a deletion in the RTI.C region that includes expressed class I genes, were more sensitive to lysis by MHC matched NK cells (PVG.IL(LEW), RT11) than were parental LEW (RT11) cells. The effect of the deletion was the opposite when MHC allogeneic (RT1c, RT1u) as well as semi‐syngeneic (RT11/c) NK cells were employed, i.e. sensitivity was decreased. We conclude that certain MHC‐encoded antigens, depending on the haplotype combination of effector and target cells, may either trigger or inhibit rat NK cell cytotoxicity. Furthermore, the potential role of peptides bound to MHC class I molecules recognized by NK cells is discussed.
AB - A major role for the nonclassical major histocompatibility complex (MHC) class I region, i.e. RTI.C, in controlling rat natural killer (NK) cell alloreactivity has recently been established, and several findings suggested the existence of NK‐triggering alloantigens coded for by this region. Here, we have extended our studies on the MHC control of NK cell cytotoxicity against concanavalin A‐activated T cell blasts by comparing semi‐syngeneic and fully allogeneic combinations, and we show the following: (a) The self MHC exerted a strong influence on the NK allorecognition repertoire. (b) When anti‐F1 hybrid cytolytic activities of parental strain NK cells were measured, both recessively and non‐recessively inherited susceptibility patterns emerged. (c) In most combinations parental strain cells were lysed by F1 hybrid NK cells, thus resembling the hybrid resistance phenomenon described in mice. The cytotoxicity was lower in strain combinations where NK susceptibility was inherited non‐recessively, i.e. when parent anti‐F1 reactivity was detected, than in recessive combinations. (d) LEW.1LM1 (RT11m1) target cells, with a deletion in the RTI.C region that includes expressed class I genes, were more sensitive to lysis by MHC matched NK cells (PVG.IL(LEW), RT11) than were parental LEW (RT11) cells. The effect of the deletion was the opposite when MHC allogeneic (RT1c, RT1u) as well as semi‐syngeneic (RT11/c) NK cells were employed, i.e. sensitivity was decreased. We conclude that certain MHC‐encoded antigens, depending on the haplotype combination of effector and target cells, may either trigger or inhibit rat NK cell cytotoxicity. Furthermore, the potential role of peptides bound to MHC class I molecules recognized by NK cells is discussed.
KW - Alloreactivity
KW - Genetics
KW - Major histocompatibility complex
KW - Natural killer cells
KW - Rats
UR - http://www.scopus.com/inward/record.url?scp=0029039964&partnerID=8YFLogxK
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U2 - 10.1002/eji.1830250518
DO - 10.1002/eji.1830250518
M3 - Article
C2 - 7774627
AN - SCOPUS:0029039964
SN - 0014-2980
VL - 25
SP - 1249
EP - 1256
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 5
ER -