Identification of B- and T-cell epitopes within the MTP40 protein of Mycobacterium tuberculosis and their correlation with the disease course

Abstract

Synthetic peptides derived from the amino acid sequence of MTP40, a recently characterized Mycobacterium tuberculosis protein, were tested by two different immunological assays in 91 individuals. For the purposes of this study, the population was distributed in four groups: active tuberculosis (TBC) patients with elevated bacillus loads (BK+), active TBC patients with low bacillus loads (BK-), healthy individuals living in the same household with tuberculous patients (HH), and normal individuals, who had presumably never been in contact with the bacilli (control). We found that T cells of individuals belonging to the HH group showed the highest and most frequent recognition of these peptides in a T-cell proliferation assay, while their antibodies showed the lowest recognition of these peptides when tested by enzyme-linked immunosorbent assay. In contrast, TBC patients revealed an inverse pattern of immune response. Interestingly, one of these peptides (P7) was recognized by T cells of 64% of the HH individuals and by 4.5% of normal donors. Another peptide (P4) was recognized by 55% of sera from BK+ patients and by 5.5% of normal donors. The results presented here indicate the existence of T-and B-cell epitopes within the MTP40 protein. Given the particular recognition pattern of this protein, added to the fact that it appears to be a species-specific antigen of M. tuberculosis, a detailed study of the immune response to it may be useful in the design of more accurate diagnostic tests and an improved vaccine against human TBC.

Determination of Lipoprotein Z-Specific IgA in Tuberculosis and Latent Tuberculosis Infection

“…Our findings demonstrate that LppZ is of high immunogenicity upon M. tb infection and several studies indicate that both humoral and cellular immune responses are involved in protection against M. tb infection (Falla et al, 1991 ; Mattos et al, 2010 ; Scriba et al, 2017 ). The observation that high levels of M. tb -specific antibodies could be detected without TST reactivity suggests that M. tb -specific antibodies could be elevated in the absence of cellular immune response (Bothamley et al, 1992 ; Sousa et al, 1997 ).…”

Evidence for a rapid rate of molecular evolution at the hypervariable and immunogenic Mycobacterium tuberculosis PPE38 gene region

“…Whether the loss of expression of these genes can, in some cases, be beneficial to the organism remains unclear but many examples of potential "virulence suppressor" genes have been documented [ 62 ]. PlcA , PPE and esx genes have all been shown to produce antigenic proteins [ 7 - 9 , 63 - 65 ] and it is conceivable that the loss of such potentially potent antigens could aid in immune escape. A recent study [ 66 ] has characterised the cellular immune response to 167 peptides representing 8 ORF's (Rv 2346c - Rv 2353c ) within the RD5 region (referred to in this study by the Behr et al [ 24 ] annotation, RD7) that is absent in M. bovis , M. caprae and M. bovis BCG compared to M. tuberculosis .…”

IgA Response to ESAT‐6/CFP‐10 and Rv2031 Antigens Varies in Patients With Culture‐Confirmed Pulmonary Tuberculosis, Healthy Mycobacterium tuberculosis–Infected and Non‐Infected Individuals in a Tuberculosis Endemic Setting, Ethiopia

“…Although both humoral and cell-mediated immune responses are involved in protection against Mtb infection [6,7], much attention has been given to the role of the latter, but little effort has been made to extensively explore the protective role of antibodies in TB. Reappraisal studies on the potential roles of antibodies in protection against TB have been recommended to better understand the components of the host immune responses against TB [8][9][10].…”