Epitope mapping of HTLV envelope seroreactivity in LGL leukaemia

Abstract

Sera from approximately 50% of patients with large granular lymphocyte (LGL) leukaemia react with a recombinant human T-cell leukaemia/lymphoma virus (HTLV) transmembrane envelope protein, p21e. Two immunodominant epitopes within env p21e have been defined by reactivity against recombinant proteins GD21 and BA21. In this study sera from 41 patients with LGL leukaemia were examined for reactivity against these recombinant HTLV env proteins. Overall, 21/41 (51%) sera reacted to p21e. Only two sera reacted to GD21. The predominant immunoreactivity against p21e was directed against the BA21 epitope, with 19/41 (46%) sera being BA21 positive. Seroconversion to BA21 protein was also documented. PCR analyses confirmed the low incidence of protypical HTLV sequences (2/41, 5%). These data document an association between BA21 seroreactivity and LGL leukaemia. This finding raises the possibility that such BA21 seroreactivity could be due to cross-reactivity to a cellular or retroviral antigen sharing some amino acid homology with the transmembrane glycoprotein of HTLV.

ERK couples chronic survival of NK cells to constitutively activated Ras in lymphoproliferative disease of granular lymphocytes (LDGL)

“…We demonstrate here that NK cells from patients with NK-LDGL have an activated phenotype, and it has been proposed that an unknown, perhaps viral, antigen is responsible for expansion of pre-LDGL NK populations (Loughran et al, 1997). Although these patients are not infected with prototypical HTLV-I or II, sera from most patients react with the BA21 epitope of the p21env protein of HTLV-I (Loughran et al, 1994(Loughran et al, , 1997Perzova et al, 2000). These data suggest that patients with NK-LDGL have been exposed to a protein homologous to BA21, perhaps by infection with a novel retrovirus.…”

“…Patients with chronic NK-LDGL have lymphocytosis that is often associated with bone marrow failure consisting of moderate anemia and/or neutropenia (Tefferi et al, 1994). Although the etiology of chronic NK-LDGL is not known, patients have high antibody titers to an envelope epitope (BA21) of HTLV-I, suggesting that the disease may be related to an HTLV-like retroviral infection (Loughran et al, 1997).…”

Large Granular Lymphocyte Leukemia

“…An association of T-cell LGL leukemia with several different autoimmune conditions supports this hypothesis. Human T-cell leukemia virus II (HTLV-II) sequences have been detected in two patients with indolent T-cell LGL leukemia [21,22]. Seroindeterminate reactivity against HTLV-I envelope (env) epitope BA21 has been described in approximately 50% of patients with CD3 + and 73% of patients with CD3 −…”

“…LGL leukemia [22,23]. Detailed amino acid analysis of BA21 revealed that a 10-amino acid peptide, PP10, was responsible for the seroreactivity [24].…”

Białaczki z dużych ziarnistych limfocytów T i komórek naturalnej cytotoksyczności

“…Jedną z nich jest przewlekła stymulacja przez antygeny wirusowe, takie jak: ludzki wirus limfotropowy (HTLV-I, human T-cell lymphotrophic virus type I) lub autoantygeny, która prowadzi do aktywacji i klonalnej ekspansji cytotoksycznych limfocytów T CD8+. U większości pacjentów wykazano obecność białka env p21e (BA 21) pochodzącego z otoczki wirusa HTLV-I [22][23][24][25].…”