Role of MHC class‐i antigens and the CD3 complex in the lysis of autologous human tumours by T‐cell clones

Abstract

Peripheral blood lymphocytes (PBL) of 4 patients with malignant effusions were stimulated for 6 days with purified autologous tumour cells, before isolation of the lymphoblasts and cloning by limiting dilution in interleukin-2 (IL-2). Forty-five clones were analyzed for cytotoxicity (CTX) against autologous, allogeneic tumour and erythromyeloid K562 cells of known status with respect to expression of major histocompatibility complex (MHC) antigens, estimated by reaction with the W6/32 (anti HLA, -A, -B, -C monomorphic) and TDR 31.1 (anti HLA-DR) monoclonal antibodies (MAb). All 45 clones were CD3+. Twenty-five (56%) of them were cytotoxic for at least one target; 24 were autoreactive (restricted in 7); 17 were alloreactive; 16 were K562 reactive. Under comparable conditions autoreactivity was partially blocked by W6/32 in 12/20 effector:target combinations; alloreactivity in 8/13 and K562 reactivity in 0/14. Modulation of effector cell surface CD3 antigens by OKT3 monitored by flow cytometry reduced autoreactivity in 9/14 combinations, alloreactivity in 2/6 and K562 reactivity in 0/4. W6/32 blocking and T3 modulation of cytotoxicity were almost invariably concordant against the same target. The data suggest that, to accomplish lysis of autologous and allogeneic tumour targets, certain clones require MHC recognition and a functional CD3 complex, while for others with similar target cell repertoires, there is no such requirement. It is possible that T-cell clones responding to a tumour-associated antigen (TAA) in the context of self MHC antigens can also respond to an allogeneic class-I product in the absence of TAA, and/or that aberrant class-I antigen expression on autologous tumours accounts for the alloreactivity.

Selective expansion of a specific anti‐tumor CD8+ cytotoxic T lymphocyte clone in the bulk culture of tumor‐infiltrating lymphocytes from a melanoma patient: Cytotoxic activity and T cell receptor gene rearrangements

“…Lysis was also inhibited by pre-incubating tumor cells with a mAb against class I MHC antigens.These results strongly suggested that the TcR was involved in killing of autologous tumor cells by the CD8+ clone and that HLA class I molecules expressed on M6 tumor cells were restricting elements of this recognition. The lytic activity of the CD8+ clones on M6 melanoma cells was higher than that reported so far for other specific CTL clones [6,9,151 with the exception of those described by Boon et al [8,141. Furthermore., lysis remained significant (30%) even at an E/T ratio of 1.…”

“…In contrast anti-melanoma CTL clones described recently needed a weekly restimulation to keep their lytic potential [4,8,14]. In previous studies CTL clones derived from PBL from cancer patients usually exhibited various levels of killing on autologous and allogeneic tumor cells [5,6,9,11,12,151.The very homogeneous cytotoxic activity of the 13 CD8+ clones studied here is probably the result of their clonal origin and support a role of the TcR in their specificity.…”

T lymphocytes can mediate lysis of autologous melanoma cells by multiple mechanisms: Evidence with a single T cell clone

“…Three different groups of CTL clones could be distinguished: one that preferentially recognizes the autologous neoplastic cells in a T-cell-receptor(TCR)-dependent, major-histocompatibility-complex(MHC)-restricted fashion [4,36]; a second one that kills autologous and allogeneic tumor cells of the same histotype [9,39], and a third one with a broad reactivity extended to neoplastic targets of different histology and without MHC-restriction or TCR involvement [27].…”

Lacking prognostic significance of β2-microglobulin, MHC class I and class II antigen expression in breast carcinomas

“…The involvement of MHC class I antigens in the in vitro lysis of tumour cells by specific cytotoxic T-lymphocytes is well documented (Anichini et al, 1985;V'anky, 1986;Roberts et al, 1987;V'anky et al, 1987;Itoh et al, 1988;Darrow et al, 1989;Knuth et al, 1989).…”