One allogeneic cytolytic T lymphocyte clone distinguishes three different HLA-B27 subtypes: identification of amino acid residues influencing the specificity and avidity of recognition.
The HLA-B27 antigen may be divided into at least three subgroups, designated HLA-B27.1, -B27.2, and -B27.3, by specific cytolytic T lymphocytes. In an attempt to explore the functional relevance of HLA polymorphism, an alloimmune cytolytic T cell clone T3+, T8+, T4- has been characterized, which displays a distinct reactivity pattern with each one of the three HLA-B27 subtypes. This cell kills both B27.1- and B27.2- but not B27.3-positive targets. Its lytic efficiency is greater with B27.1 than with B27.2 cells. The clone does not recognize either B7-positive targets or most B27-negative cells. But HLA-B40-bearing cells are lysed, albeit with significantly less efficiency than any B27-positive targets. The differences in killing ability for B27.1, B27.2, and B40 are also evident in cold-target inhibition studies, indicating that a) B27.1 cells can efficiently inhibit lysis of B27.2 and B40 targets, b) B27.2 cells inhibit the lysis of B40 but not of B27.1 targets, and c) B40 cells do not inhibit B27.1 or B27.2 target lysis. In addition, anti-T3 and anti-T8 antibodies are much more effective in inhibiting the lysis of B27.2 targets than that of B27.1-positive cells, suggesting that the observed differences in killing efficiency of the various targets are due to the fact that the tightness of the effector-target interaction is affected by the structural changes between the different HLA antigens. A correlation of the reactivity pattern of this T cell clone with the known amino acid sequences of the HLA-B27, HLA-B40, and HLA-B7 antigens suggests that the clone recognizes a conformational determinant contributed to by residues within the segments 149-156 and 67-83. Those in the former segment appear to be an essential portion of this determinant, whereas polymorphism in the region 67-83 has a modulating effect on the reactivity of the effector but does not abrogate recognition.
Aparicio
P
P
Vega
M A
MA
López de Castro
J A
JA
D000596:Amino Acids / Q000032:analysis*; D000911:Antibodies, Monoclonal / Q000502:physiology; D000915:Antibody Affinity; D000954:Antigens, Surface / Q000276:immunology; D001667:Binding, Competitive; D002999:Clone Cells / Q000145:classification / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D000939:Epitopes / Q000032:analysis / Q000276:immunology*; D006680:HLA Antigens / Q000145:classification / Q000235:genetics / Q000276:immunology*; D015796:HLA-B27 Antigen; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology*
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D006680:HLA Antigens; D015796:HLA-B27 Antigen