CD4+ BINDING PROTEINS AS IMMUNOSUPPRESSION FACTORS

gp120的C4构象变化欺骗了针对HIV的免疫反应。我们从gp120的C4结构域合成了一种螺旋和环状两种形式的肽。我们了解到，尽管这两种形式具有相同的氨基酸序列和结合重组可溶性CD4的能力，但它们具有非常不同的生物学和免疫学特性。当在兔体内使用具有α螺旋构象的C4肽体作为免疫原时，可以形成抗体与亲本gp120反应，但抗体不能阻断gp120与CD4的结合，并且在体外不能抑制HIV感染。兔抗C4肽体抗体不能阻断Jurkat细胞对conconavalin a的gp120抑制IL-2的产生，10个HIV阳性的人血清中有9个确实含有与C4肽体以螺旋构象反应的抗体。今年我们了解到，当环C4肽在兔子体内用作免疫原时，会形成抗体，与亲本gp120反应，这些抗体确实阻止gp120与CD4结合，并在体外抑制HIV感染。抗环C4抗体降低了gp120对conconavalin a反应的Jurkat细胞IL-2产生的衰减量，只有1 / 10的HIV阳性人血清中含有与C4环化肽反应的抗体。综上所述，自然的HIV感染导致产生针对线状和/或螺旋状C4肽的抗体，但为了具有保护作用，抗体应该针对C4的环状构象。因此，C4从环状到螺旋的构象转变允许gp120避开中和性免疫反应。通过这种方式避免免疫监视，gp120可以结合到细胞表面CD4而不被抗体阻断。最终结果代表了HIV保护自身免受免疫系统破坏的另一种方式。环化形式的C4肽目前正在开发中，作为一种免疫原，将纳入未来的艾滋病毒疫苗配方中，并作为一种免疫疗法，为缺乏这些特异性抗体的艾滋病毒阳性个体提供中和性抗C4抗体。- CD4，免疫抑制，gp120， HIV，疫苗，T细胞，口腔癌，IL-2，多肽，构象

A conformational change in C4 of gp120 fools the immune response against HIV. We synthesized a peptide from the C4 domain of gp120 in 2 forms – helical and cyclic. We learned that both forms, although having the same amino acid sequence and ability to bind recombinant soluble CD4, have very different biological and immunological properties. When the C4 peptomer having an alpha helical conformation is used as the immunogen in rabbits, antibodies are formed that react with the parent gp120 but the antibodies do not block gp120 binding to CD4 and they do not inhibit HIV infection in vitro. Rabbit anti C4 peptomer antibodies did not block the gp120 attenuation of IL-2 production by Jurkat cells in response to conconavalin A. 9 out of 10 human sera that were HIV+ do contain antibodies that react with the C4 peptomer in the helical conformation. This year we learned that, when the cyclic C4 peptide is used as an immunogen in rabbits, antibodies are formed that react with the parent gp120 and these antibodies do block gp120 binding to CD4 and they do inhibit HIV infection in vitro. Anti cyclic C4 antibodies decreased the amount that gp120 attenuates IL-2 production by Jurkat cells responding to conconavalin A. Only 1 out of 10 HIV+ human sera that were tested contained antibodies that reacted with the C4 cyclized peptide. In summary, natural HIV infection causes the production of antibodies against the linear and/or helical C4 peptide but, in order to be protective, the antibodies should be against the cyclic or looped conformation of C4. Thus, a conformation shift from loop to helix by C4 allows gp120 to dodge a neutralizing immune response. By avoiding immune surveillance this way, gp120 can bind to cell surface CD4 without being blocked by antibodies. The end result represents another way HIV protects itself from destruction by the immune system. The C4 peptide in the cyclized form now is being developed as an immunogen to be included in future HIV vaccine formulations and as an immunotherapeutic to provide neutralizing anti C4 antibodies to HIV+ individuals who are lacking these specific antibodies. - CD4, immunosuppression, gp120, HIV, vaccine, T cells, oral cancer, IL-2, peptides, conformation