Regulation of T helper-B lymphocyte adhesion through CD4-HLA class II interaction.
Antigen-independent adhesion of CD4+ T lymphocytes to Epstein-Barr virus (EBV)-transformed B cells is mediated by CD2/lymphocyte function-associated antigen (LFA)-3 and LFA-1/intracellular adhesion molecule (ICAM)-1. Although some anti-CD4 antibodies block the antigen-independent adhesion of CD4+ T lymphocytes, the CD4-HLA class II interaction does not appear to significantly contribute to the forces of cell adhesion since CD4+ T cells equally bind HLA class II+ and HLA class II- mutant B cells. In addition, conjugates formed between CD4+ T cells and HLA class II- B cells remain stable for at least 1 h while CD4+T/HLA class II+ B cell conjugate percentages promptly drop off. Down-regulation of CD4 or spontaneous low expression of CD4 also results in a persistance of conjugates formed with B cells. The role of the CD4-HLA class II interaction has been further studied by investigating the inhibitory effect of synthetic 12-mer peptides analogous to HLA class II and containing the Arg-Phe-Asp-Ser sequence conserved in the beta 1 domain. These peptides were previously found to inhibit HLA class II-restricted T cell responses, this sequence being thought to be involved in CD4-HLA class II interaction. These peptides block conjugate formation of CD4+ resting T cells or clones but not of CD8+ T cells, by interacting with the T cells as shown by preincubation experiments. Down-regulation of CD4 or spontaneous low expression results in the loss of the inhibitory activity. The peptide-mediated inhibition is neutralized by a soluble dimeric CD4 molecule. Alteration within the Arg-Phe-Asp-Ser sequence results in a significant loss of inhibition. It is thus proposed that the CD4-HLA class II interaction negatively regulates antigen-independent adhesion of T cells, this interaction involving the highly conserved Arg-Phe-Asp-Ser sequence in the HLA class II beta 1 sequence as a CD4-binding site.
Mazerolles
F
F
Immunologie et Rhumatologie Pédiatriques, INSERM U132, Hôpital des Enfants-Malades, Paris, France.
Amblard
F
F
Lumbroso
C
C
Lecomte
O
O
Van de Moortele
P F
PF
Barbat
C
C
Piatier-Tonneau
D
D
Auffray
C
C
Fischer
A
A
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015704:CD4 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D006681:HLA-D Antigens / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008211:Lymphocyte Cooperation; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D013329:Structure-Activity Relationship; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology
D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D006681:HLA-D Antigens; D010455:Peptides