Current knowledge on the structure of
lipoarabinomannan (
LAM) has resulted primarily from detailed studies on a few selected laboratory strains of Mycobacterium tuberculosis, Mycobacterium bovis BCG, and Mycobacterium smegmatis. Our previous work was the first to report on the salient structural features of M.
tuberculosis clinical isolates and demonstrated significant structural variations. A prime effort is to correlate a particular structural characteristic with observed differences in eliciting an immunobiological response, especially in the context of CD1-restricted presentation of
LAM to T cells. T cell clones derived from the cutaneous lesions of
leprosy patients have been shown to recognize specifically
LAM from Mycobacterium leprae and not from M.
tuberculosis Erdman or H37Rv. Herein we provide further fine structural data on
LAM from M. leprae (LepLAM) and a
tuberculosis clinical isolate, CSU20 (CSU20LAM), which was unexpectedly recognized by the supposedly LepLAM-specific CD1-restricted T cell clones. In comparison with the de facto laboratory
LAM standard from M.
tuberculosis H37Rv (RvLAM), LepLAM derived from in vivo grown M. leprae is apparently simpler in its
arabinan architecture with a high degree of exposed, non-
mannose-capped termini. On the other hand, CSU20, an
ethambutol-resistant clinical isolate, makes a vastly heterogeneous population of
LAM ranging from rather small and non-
mannose-capped to full-length and fully capped variants. LepLAM and CSU20LAM contain a higher level of succinylation than RvLAM, which, in the context of truncated or less elaborated
arabinan, may contribute to selective recognition by T cells.
LAM from all species could be resolved into discrete forms by isoelectric focusing based apparently on their
arabinan heterogeneity. In the light of our current and more recent findings, we reason that all immunobiological data should be cautiously interpreted and that the actual
LAM variants that may be present in vivo during
infection and pathogenesis need to be taken into consideration.