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J van Embden

Publications and source records attributed to J van Embden.

7 recordsLinked to original sources
PubMed1991

Mycobacterial heat-shock proteins as carrier molecules.

We have previously shown that the priming of mice with live Mycobacterium tuberculosis var. bovis (Bacillus Calmette-Guérin, BCG) and immunization with the repetitive malaria synthetic peptide (NANP)40 conjugated to purified protein derivative (PPD), led to the induction of high and long-lasting titers of anti-peptide IgG antibodies, overcoming the requirement of adjuvants and the genetic restriction of the antibody response to the peptide (Lussow et al., Proc. Natl. Acad. Sci. USA 1990. 87:2960). This initial work led us to the following observations. BCG had to be live for priming to lead to the induction of anti-peptide antibodies. Surprisingly, priming with other living microorganisms which chronically infect the macrophage (e.g. Salmonella typhimurium and Leishmania major) also induced anti-peptide antibodies in mice immunized with PPD-(NANP)40 conjugate. It was, thus, hypothesized that molecules expressed during active infection and also known to be highly conserved between species, namely the heat-shock proteins (hsp), could mediate the T cell sensitization required for the production of anti-peptide antibodies. In fact, when the PPD protion of the conjugate was replaced by a highly purified recombinant protein corresponding to the 65-kDa (GroEL-type) hsp of M. bovis, this resulted in the production of anti-(NANP) IgG antibodies in BCG-primed mice, irrespective of the major histocompatibility complex-controlled responsiveness to the (NANP) sequence itself. Further, similar induction of anti-peptide antibody response was also obtained with a recombinant 70-kDa (DnaK-type) hsp of M. tuberculosis, but not with a small molecular mass (18 kDa) of M. leprae. Finally, an adjuvant-free carrier effect for anti-peptide IgG antibody production in BCG-primed mice, was also exerted by the GroEL hsp of Escherichia coli. This finding that hsp can act as carrier molecules without requiring conventional adjuvants is of potential importance in the development of vaccine strategies.

Adjuvants, Immunologic↗
PubMed1990

Synovial cells responding to a 65-kDa mycobacterial heat shock protein have a high proportion of a TcR gamma delta subtype uncommon in peripheral blood.

We have analysed the ability of T cells from synovial fluid mononuclear cells (SFMC) and from peripheral blood mononuclear cells (PBMC) of inflammatory arthritic diseases to proliferate in response to mycobacterial antigens (65-kDa heat shock protein [hsp] of BCG, whole BCG) and to rat collagen type II. The SFMC demonstrated a significantly greater ability to respond to 65-kDa hsp of BCG, and to whole BCG, compared with PBMC from the same patients. With collagen type II, only a small proportion of the patients showed a proliferative response, although with this antigen also SFMC responded better than PBMC. There was no difference between SFMC and PBMC in the response to control antigen (tetanus toxoid), phytohaemagglutinin (PHA), or interleukin 2 (IL-2). A high proportion of cells in SFMC-derived short-term T-cell lines were of TcR gamma delta type, often exceeding the number of TcR gamma beta type. There was a significantly higher proportion of TcR gamma delta cells in the SFMC lines compared with the PBMC lines, and a large part of the TcR gamma delta cells in the SFMC cultures was CD8+. The SFMC lines had a high proportion of delta-TCS-1+ cells (V delta 1) among their TcR gamma delta cells, always exceeding the percentages of Ti gamma A+(V gamma 9) and BB3+ (V delta 2). In the PBMC lines, the distribution of TcR gamma delta subtypes was markedly different, with a Ti gamma A+/BB3+ population in the majority. These data argue for a different subpopulation distribution of TcR gamma delta cells in synovial fluid compared with peripheral blood of patients with inflammatory arthritic diseases.

Antigens, Bacterial↗
PubMed1986

A recombinant 64 kilodalton protein of Mycobacterium bovis bacillus Calmette-Guerin specifically stimulates human T4 clones reactive to mycobacterial antigens.

A recombinant 64 kD protein of Mycobacterium bovis bacillus Calmette-Guerin (BCG) (antigen A), which amounted to approximately 2% of an E. coli lysate, was tested for its capacity to stimulate human T4 clones reactive to mycobacterial proteins. Two out of four crossreactive clones, established from a patient with tuberculoid leprosy, which could be stimulated by protein preparations of M. leprae and M. tuberculosis, and by particulate M. bovis BCG were also reactive to antigen A without further enrichment from E. coli lysate. In addition, BCG-reactive T cell clones from two of three healthy PPD+ donors reacted with antigen A. This finding shows that human T cell clones may be useful for probing gene-cloned proteins of potential value for vaccination against diseases where protection is mediated exclusively by T cells.

Clone Cells↗