Structural polymorphism of the human platelet Fc gamma receptor.
A variable T lymphocyte proliferative response to murine IgG1 anti-T3 monoclonal antibodies, in which most North American Caucasians respond whereas a minority do not, is well established. This is most likely the result of a genetic polymorphism manifested by 1) the inability of the monocyte 40-kDa IgG FcR of some individuals to bind murine IgG1, and 2) a distinctive trimorphic pattern on IEF of the monocyte 40-kDa FcR, one form being seen in all individuals who do not respond and another form (or a combination of both forms) being seen in those who do respond. We have evaluated the IEF patterns of the platelet 40-kDa FcR and find that in every individual tested the pattern for platelet FcR correlates with that seen for the monocyte 40-kDa FcR pattern. Furthermore, the platelets of those individuals whose "nonresponder" monocyte 40-kDa FcR did not mediate a murine IgG1 anti-T3 response did not respond with an aggregation reaction to murine IgG1 immune complexes (opsonized E). In contrast, platelets from donors possessing "responder" monocytes displayed positive "aggregation" responses to E coated with murine IgG1 antibody. However, the platelet FcR structural polymorphism described earlier did not correlate with the donor-specific variability in capacity of platelets to respond functionally to aggregated human IgG described in an earlier paper. Rather, the variation in capacity of platelets from individual donors to respond functionally to aggregated human IgG was related to the quantitative expression of platelet FcR. These data indicate that the molecular mechanisms responsible for the platelet 40-kDa FcR structural polymorphism are quite different from the mechanisms governing the variation in quantitative expression of the receptor.
Looney
R J
RJ
Department of Medicine, University of Rochester Medical Center, NY 14642.
Anderson
C L
CL
Ryan
D H
DH
Rosenfeld
S I
SI
D000818:Animals; D000943:Antigens, Differentiation / Q000302:isolation & purification*; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism* / Q000502:physiology; D007525:Isoelectric Focusing; D051379:Mice; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism; D010974:Platelet Aggregation; D011110:Polymorphism, Genetic; D011961:Receptors, Fc / Q000302:isolation & purification*; D017452:Receptors, IgG; D013329:Structure-Activity Relationship
D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG