The helper T-cell repertoire of mice expressing class II major histocompatibility complex beta chains in the absence of alpha chains.
Mutant mice generated by disrupting the H2-Aab major histocompatibility complex (Mhc) gene are demonstrated here to express Abetab chains in the absence of alpha chains. These mice possess a CD4(+) helper T cell (Th) repertoire that uses predominantly the Vbeta7 T-cell antigen receptor (Tcr) segment for recognition of any protein antigen presented by the alpha-free Abeta molecule. As an alloantigen, the Aalpha-free Abeta molecule is recognized very poorly by T cells from a series of class II disparate mouse strains, indicating that it is grossly different from normal alpha/beta heterodimers. Indeed, molecular modeling suggests a beta/beta homodimer arrangement with an altered geometry of the Tcr contact area. Interestingly, the mutant mice exhibit normal alloreactivity, without a restricted Vbeta usage, toward a series of foreign alpha/beta class II heterodimers, although their T cells developed in the absence of such heterodimers. Thus, the complementarity of Tcr to normal alpha/beta heterodimers, and thereby also alloreactivity, appears to be an ontogeny independent (i. e., germline-encoded) feature.
Vidović
D
D
Department of Immunology, Preclinical Research, Hoffmann-La Roche, Inc., 340 Kingsland Street, Nutley, NJ 07110, USA.
Boulanger
N
N
Kuye
O
O
Toral
J
J
Ito
K
K
Guenot
J
J
Bluethmann
H
H
Nagy
Z A
ZA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008211:Lymphocyte Cooperation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008958:Models, Molecular; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta