The inositol 5-phosphatase SHIP-1 and adaptors Dok-1 and 2 play central roles in CD4-mediated inhibitory signaling.

CD4 functions to enhance the sensitivity of T cells to antigenic peptide/MHC class II. However, if aggregated in isolation, e.g.

The conundrum of inhibitory signaling by ITAM-containing immunoreceptors: potential molecular mechanisms.

Immunoreceptor signals must be appropriately transduced and regulated to achieve effective immunity while controlling inflammation and autoimmunity. It is generally held that these processes are mediated by the interplay of distinct activating and inhibitory receptors via conserved activating (ITAM) and inhibitory (ITIM) signaling motifs. However, recent evidence indicates that under certain conditions incomplete phosphorylation of ITAM tyrosines leads to inhibitory signaling.

MPYS, a novel membrane tetraspanner, is associated with major histocompatibility complex class II and mediates transduction of apoptotic signals.

Although the best-defined function of type II major histocompatibility complex (MHC-II) is presentation of antigenic peptides to T lymphocytes, these molecules can also transduce signals leading alternatively to cell activation or apoptotic death. MHC-II is a heterodimer of two transmembrane proteins, each containing a short cytoplasmic tail that is dispensable for transduction of death signals. This suggests the function of an undefined MHC-II-associated transducer in signaling the death response.

Effects of virus burden and chemokine expression on immunity to SHIV in nonhuman primates.

HIV-1 vaccine candidates are designed to elicit Type 1 immune responses, including cytotoxic T cells and neutralizing antibodies. The type of immune response is influenced by many factors, including the levels of antigen expression and production of cytokines or chemokines; we designed a nonhuman primate study to evaluate the influence of these factors on protective immunity. Recombinant SHIV were engineered to express macrophage inflammatory protein-1 alpha (MIP-1alpha), regulated upon activation, normal T-cell expressed and secreted (RANTES), or Lymphotactin (Ltn) in place of nef in SHIV(89.

Simian/human immunodeficiency virus(89.6) expressing the chemokine genes MIP-1alpha, RANTES, or lymphotactin.

We constructed replication competent, attenuated, nef-deleted SHIV(89.6) that express the rhesus macaque chemokine genes MIP-1alpha, RANTES, or LTN from the nef region. The chemokine inserts were stable during several passages in CEMx174 cells and the viruses grew well in activated rhesus PBMC.