The 14,000-molecular-weight antigen of Mycobacterium tuberculosis is related to the alpha-crystallin family of low-molecular-weight heat shock proteins

Abstract

Eight monoclonal antibodies (MAbs) directed against the 14,000-molecular-weight (14K) antigen of Mycobacterium tuberculosis reacted specifically with mycobacteria of the M. tuberculosis complex. The nucleotide sequence of the gene encoding the 14K antigen was determined by using recombinant DNA clones isolated from lambda gt11 and cosmid libraries of the M. tuberculosis genome. The DNA sequence of the 14K protein gene coded for a polypeptide of 144 amino acids with a calculated molecular mass of 16,277 Da. The 14K antigen has a marked homology with proteins belonging to the alpha-crystallin family of low-molecular-weight heat shock proteins, which includes the 18K antigen of M. leprae. The eight MAbs recognized at least four distinct epitopes localized within the following three regions of the 14K protein: amino acids 10 to 92 (MAbs F67-8 and F67-16), amino acids 41 to 92 (F159-1 and F159-11), and amino acids 41 to 144 (F23-41, F24-2, F23-49, and TB68).

Regulation of theMycobacterium tuberculosishypoxic response gene encoding α-crystallin

“…MTB Acr was originally described as a dominant antigen, frequently recognized by TB patient sera (19,20). Further evidence of its role in TB pathogenesis comes from studies showing that Acr is needed for the growth of MTB in cultured macrophages (9).…”

Human T‐ and B‐Cell Reactivity to the 16 kDa α‐Crystallin Protein of Mycobacterium tuberculosis

“…It suppresses the thermal aggregation of citrate synthase at 40ЊC, indicating that it can operate as a chaperone in vitro. Although classified as a heatshock protein [8], a widely distributed class of proteins, the 16 kDa antigen has not been detected outside Mycobacterium bovis bacillus Calmette-Guérin (BCG) or the M. tuberculosis complex [6,9], consistent with a unique role in the physiology of M. tuberculosis. These attributes of immunodominance, predominant expression during mycobacterial dormancy and species specificity make it a highly attractive candidate for the study of the immune response in humans, both from the point of view of protective immunity and the development of novel immunodiagnostic reagents.…”

The 16-kDa α-crystallin (Acr) protein ofMycobacterium tuberculosisis required for growth in macrophages

“…The Acr protein is found only in mycobacteria of the closely related tuberculosis complex, although a related protein has been found in M. leprae (13,14). Acr is known to be expressed during human infection with virulent strains of MTB because 85% of sera from patients with pulmonary tuberculosis recognized this protein (15,16).…”