Mycoplasma arthritidis mitogen. V beta engaged in mice, rats, and humans, and requirement of HLA-DR alpha for presentation.
OBJECTIVE
Mycoplasma arthritidis mitogen (MAM) is mitogenic for mouse, rat, and human T cells, and behaves as a superantigen in mice through its capacity to bind to the alpha chain of I-E molecules and engage entire sets of T cells expressing specific V beta. Here, we have attempted to fully characterize the V beta-engaging activities of MAM in mice, and define similar activities in rats and humans.


METHODS
Multiprobe RNase-protection assays and mice transgenic for human DR alpha, DR beta, and DR alpha beta were utilized for this purpose.


RESULTS
MAM-reactive V beta in the mouse included not only the previously reported V beta 6, V beta 8.1, V beta 8.2, and V beta 8.3, but also V beta 5.1. In the rat, engagement of V beta 5.1, V beta 6, V beta 8.1, and V beta 8.2, but not V beta 8.3, was documented, whereas in humans, the engaged V beta included primarily V beta 19.1 (alternatively termed V beta 17.1) and, to a lesser extent, V beta 3.1, V beta 11.1, V beta 12.1, and V beta 13.1. In DR transgenic E alpha- E beta- mice, presentation of MAM and engagement of specific V beta was effected by DR alpha.


CONCLUSIONS
Homologous V beta are engaged by MAM in mice, rats, and humans, presumably through a binding site similar to that proposed previously for other superantigens. MAM presentation primarily via the nonpolymorphic DR alpha makes it unlikely that there is involvement of such a superantigen in the pathogenesis of autoimmune diseases known to be associated with certain DR haplotypes. The possibility cannot be excluded, however, that superantigen-activated T cells may lead to disease by cross-reactions with self-antigens presented by particular DR haplotypes.
Baccala
R
R
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Smith
L R
LR
Vestberg
M
M
Peterson
P A
PA
Cole
B C
BC
Theofilopoulos
A N
AN
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens; D000942:Antigens, Bacterial; D001665:Binding Sites; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007135:Immunoglobulin Variable Region; D051379:Mice; D008808:Mice, Inbred CBA; D008934:Mitogens / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D011506:Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D018089:Superantigens
D000941:Antigens; D000942:Antigens, Bacterial; D006684:HLA-DR Antigens; D007135:Immunoglobulin Variable Region; D008934:Mitogens; C052996:Mycoplasma arthritidis mitogen; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens