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C Janeway

Publications and source records attributed to C Janeway.

At least 19 recordsLinked to original sources
PubMed2000

Innate immunity.

Explore the source record for details and available documents.

Animals↗
PubMed2000

Fly immunity: great expectations.

Preliminary analysis of the Drosophila genome sequence reveals important similarities and differences between the functioning of mammalian and invertebrate immune systems.

Animals↗
PubMed2000

The Toll receptor family and microbial recognition.

The survival of multicellular organisms is dependent on their ability to recognize invading microbial pathogens and to induce a variety of defense reactions. Recent evidence suggests that an evolutionarily ancient family of Toll-like receptors plays a crucial role in the detection of microbial infection and the induction of immune and inflammatory responses.

Animals↗
PubMed2000

Innate immune recognition: mechanisms and pathways.

The innate immune system is an evolutionarily ancient form of host defense found in most multicellular organisms. Inducible responses of the innate immune system are triggered upon pathogen recognition by a set of pattern recognition receptors. These receptors recognize conserved molecular patterns shared by large groups of microorganisms. Recognition of these patterns allows the innate immune system not only to detect the presence of an infectious microbe, but also to determine the type of the infecting pathogen. Pattern recognition receptors activate conserved host defense signaling pathways that control the expression of a variety of immune response genes.

Amino Acid Sequence↗
PubMed1998

Exogenously provided peptides of a self-antigen can be processed into forms that are recognized by self-T cells.

Major histocompatibility complex (MHC) class II molecules can present peptides derived from two different sources. The predominant source of peptide in uninfected antigen presenting cells (APCs) is from self-proteins that are synthesized within the cell and traffic through the MHC class II compartment. The other source of antigen is endocytosed proteins, which includes both self- and foreign proteins. Foreign protein antigens generate adaptive immune responses, whereas self-peptides stabilize the MHC class II heterodimer on the cell surface, allowing positive and negative selection of thymocytes. Therefore, self-antigens play an important normal role in shaping the T cell receptor repertoire as well as a pathological role in autoimmunity. To determine whether processing and presentation of self-antigens by MHC class II molecules differs depending on whether the antigen is supplied through synthesis within the cell or by endocytosis, we used a T cell clone against an Ealpha peptide presented by I-Ab to show that processing through these two routes can differ. We also show that mice can be tolerant to the epitope formed through the endogenous route, but responsive to the epitope that can be formed through endocytosis. This suggests that negative selection occurs primarily against antigens that are synthesized within the APC, and that endocytosed self-antigens could serve as autoantigens. Finally, we also demonstrate that lipopolysaccharide-activated B cells are defective for uptake, processing, and presentation of this self-antigen, and that this correlates with the increased expression of the costimulatory molecules B7.1 and B7.2. This may provide a model for studying the onset of an autoimmune response.

Animals↗
PubMed1998

Signalling initiated with CD4-TCR or TCR-TCR interactions: comparison of tyrosine phosphorylation patterns and CD45 effects.

Antigen-triggered response in T cells is mediated by the T cell receptor (TCR)/CD3-complex. This signalling, however, is modulated by a number of other surface molecules. Among the most important of these is the CD4/CD8 molecule which associates with the TCR/CD3-complex and binds to the MHC complex. The molecular mechanisms involved in interactions between TCR-TCR and TCR-CD4 are not fully understood. We have earlier described an experimental model that allows us to dissect signals involving CD4-TCR interactions and those involving TCR-TCR interactions using a mouse CD4-CD8- T cell hybridoma cell-line transfected either with the TCR from a mouse T-helper 2 cell-line (D10) alone or with both the TCR and the CD4 molecule. To further characterize these two different modes of signalling in T lymphocytes we have studied the tyrosine phosphorylation patterns resulting from these interactions. In addition, we have studied the modulatory effect of the CD45 molecule on these interactions. In contrast to some earlier reports, we found that both the patterns of induced tyrosine phosphorylation and the effects of CD45 modulation were essentially similar in the CD4-TCR and the TCR-TCR signal transduction cascades. The results are consistent with a purely synergistically amplifying function for CD4 on the TCR-mediated signalling.

Animals↗
PubMed1995

Cloning and expression of a Leishmania donovani gene instructed by a peptide isolated from major histocompatibility complex class II molecules of infected macrophages.

The studies reported here describe the isolation of peptides from MHC class II molecules of murine macrophages infected with Leishmania donovani, and the use of the derived peptide sequences to rescue the pathogen peptide donor protein. The isolation of the peptides was carried out by comparing the RP HPLC profile of peptides extracted from infected macrophages with the peptides extracted from noninfected cells. Several distinct HPLC peaks unique to infected macrophages were sequenced. One of the peptides that was not homologous to any known protein was used to instruct the designing of an oligonucleotide sense primer that was used in combination with an oligo dT nucleotide (anti-sense primer) to amplify by PCR a DNA fragment from L. donovani cDNA. The amplified DNA fragment was cloned and used as a probe to screen a L. donovani cDNA library. The cloned gene (Ld peptide gene) has an open reading frame of 525 bp and has no homology with any known protein/gene sequence. Northern blot analyses indicated that the Ld peptide/gene is broadly distributed and expressed among species of the Leishmania genus, in both the amastigote and promastigote life cycle forms. Using the pGEX 2T vector, the gene was expressed and the relationship of the purified recombinant protein with L. donovani was confirmed using both antibody and T cell responses from immunized or infected animals. The gene encodes a 23-kD molecule (Ldp 23) associated with the cell surface of L. donovani promastigotes. In addition, T cells purified from the lymph nodes of BALB/c mice immunized with L. donovani or infected with L. major, and from CBA/J mice infected with L. amazonensis were stimulated to proliferate by the recombinant Ldp 23 and produced high levels of IFN-gamma and no IL 4. This observation suggests that the Ldp 23 is an interesting parasite molecule for the studies concerning the host/parasite interaction because the Th1 pattern of cytokine response that it induces is correlated with resistance to Leishmania infections. These results clearly point to an alternative strategy for the purification of proteins useful for the development of both vaccines and immunological diagnostic tools not only against leishmaniasis but also for other diseases caused by intracellular pathogens.

Amino Acid Sequence↗
PubMed1994

Anti-CD45 augments response of a Th2 clone to TCR cross-linking.

The CD45 molecule is a transmembrane tyrosine phosphatase that may be associated with the T-cell receptor (TCR). This has led to the suggestion that CD45 may be important for the regulation of signal transduction in T cells. This idea is supported by the finding that antibodies against CD45 are comitogenic in proliferation assays. In the present work, we have examined the comitogenicity of CD45 antibodies by studying the effect of CD45, CD45RA, and CD45RB monoclonal antibodies (MoAbs) on proliferation of D10 cells induced with T-cell receptor (TCR) MoAbs. In addition interactions with some other proliferation inducing agents namely CD3 antibodies, lectins, and IL-2, are examined here. We have found that in general the CD45 MoAbs would significantly enhance proliferation induced by a wide spectrum of TCR MoAbs and other proliferation inducing agents, with some minor quantitative differences. The CD45 and CD45RB MoAbs were equally potent in their comitogenic activity while the CD45RA antibody was somewhat less potent. The comitogenic effect was maximal when CD45 antibodies were added simultaneously with the TCR MoAb, but significant comitogenicity could be detected when CD45 MoAbs were added up to 24 h after the initiation of the culture indicating that the CD45 antibodies also affect other processes than the initial signal transduction cascade.

Animals↗
PubMed1989

Immunogenicity signals 1,2,3 ... and 0.

The most critical property of the immune system is its ability to discriminate self from nonself. Failure to respond to nonself can lead to overwhelming infection, while failure in the ability not to respond to self, or self tolerance, leads to autoimmunity. A meeting held in Steamboat Springs focused on this issue under the title of 'Immunogenicity'. This brief summary focuses on one of the key issues considered at this conference - the signals involved in the induction of lymphocyte activation. In addition, an hypothesis of immune system function that appears to follow from these findings is described.

Humans↗
PubMed1988

Molecular analysis of T cell receptor gamma gene expression in allo-activated splenic T cells of adult mice.

Northern analysis, hybridization in situ and cDNA sequence analysis have been used to demonstrate that the induction of T cell gamma-gene expression is a general occurrence when primary splenic T cells of adult mice are cultured in short-term mixed lymphocyte reactions (MLR). Splenic T cells from nine strains of mice examined in eleven different MLR all showed significant induction of gamma-RNA, even when the primary T cell response was to only a three amino acid mismatch in a major histocompatibility complex class I antigen. In MLR examined in detail, the expression is highly enriched for in CD3+ "double-negative" T cells (lacking both CD4 and CD8 expression). A cDNA sequence analysis, constituting the first such analysis of any size of gamma-gene transcripts from circulating, peripheral cells of adult mice, revealed transcription to be frequently of productively rearranged genes. These genes display extensive junctional diversity.

Animals↗