The role of the B7-1a molecule, an alternatively spliced form of murine B7-1 (CD80), on T cell activation.
B7 molecules (CD80 (B7-1) and CD86 (B7-2/B70)) on APCs provide costimulatory signals for T cell proliferation. We previously described the presence of an alternatively spliced form of murine CD80 (previously termed MB7-2 and renamed as B7-1a) that completely lacks the second Ig-like domain coded by exon 3 in activated murine B cells. in this study, we first examined whether B7-1a mRNA can be detected in vivo by RNase protection assay. The expression of B7-1a mRNA was only detected in lymphoid organs although the level of expression was lesser than that of CD80 mRNA. However, we demonstrated that the expression of B7-1a mRNA like CD80 mRNA was considerably augmented in spleen cells treated with either LPS in vitro or OVA/CFA conjugate in vivo. We next determined the functional activity of B7-1a using Chinese hamster ovary (CHO) cells transfected by B7 genes. When resting T cells were cocultured with CHO cells expressing B7-1a molecules in the presence of PMA/ionomycin, T cell proliferation was not detected, while CHO cells either expressing CD80 or CD86 could promote the proliferation of resting T cells. in contrast to resting T cells, CHO cells expressing B7-1a could support the proliferation of activated T cells. Thus, costimulatory activity of B7-1a molecules was dependent upon the activation stage of T cells. Therefore the IgV-like region of CD80 contains a critical region for functional interaction with its ligands and can transduce a costimulatory signal for T cell proliferation.
Inobe
M
M
Section of Immunopathogenesis, Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Aoki
N
N
Linsley
P S
PS
Ledbetter
J A
JA
Abe
R
R
Murakami
M
M
Uede
T
T
D017398:Alternative Splicing / Q000276:immunology*; D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D008213:Lymphocyte Activation / Q000187:drug effects*; D008221:Lymphoid Tissue / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D018122:B7-1 Antigen; D012333:RNA, Messenger