The 1469 marriage of Isabella I of Castile and Ferdinand II of Aragon and the 1479 death of John II of Aragon led to the creation of modern-day Spain. In 1492, Granada was captured from the Moors, thereby completing the Reconquista. Portugal had during the 15th century particularly under Henry the Navigator gradually explored the coast of Africa, and in 1498, Vasco da Gama found the sea route to India. The Spanish monarchs met the Portuguese challenge by financing the expedition of Christopher Columbus to find a western sea route to India, leading to the discovery of the Americas in 1492.
When was modern-day Spain created?
1492

Between 1631 and 1890, the city tripled its area through land reclamation by filling in marshes, mud flats, and gaps between wharves along the waterfront. The largest reclamation efforts took place during the 19th century; beginning in 1807, the crown of Beacon Hill was used to fill in a 50-acre (20 ha) mill pond that later became the Haymarket Square area. The present-day State House sits atop this lowered Beacon Hill. Reclamation projects in the middle of the century created significant parts of the South End, the West End, the Financial District, and Chinatown. After The Great Boston Fire of 1872, workers used building rubble as landfill along the downtown waterfront. During the mid-to-late 19th century, workers filled almost 600 acres (2.4 km2) of brackish Charles River marshlands west of Boston Common with gravel brought by rail from the hills of Needham Heights. The city annexed the adjacent towns of South Boston (1804), East Boston (1836), Roxbury (1868), Dorchester (including present day Mattapan and a portion of South Boston) (1870), Brighton (including present day Allston) (1874), West Roxbury (including present day Jamaica Plain and Roslindale) (1874), Charlestown (1874), and Hyde Park (1912). Other proposals, for the annexation of Brookline, Cambridge, and Chelsea, were unsuccessful.
What sits on Beacon Hill today?
State House

In the mid-1950s, Frank Burnet, inspired by a suggestion made by Niels Jerne, formulated the clonal selection theory (CST) of immunity. On the basis of CST, Burnet developed a theory of how an immune response is triggered according to the self/nonself distinction: "self" constituents (constituents of the body) do not trigger destructive immune responses, while "nonself" entities (e.g., pathogens, an allograft) trigger a destructive immune response. The theory was later modified to reflect new discoveries regarding histocompatibility or the complex "two-signal" activation of T cells. The self/nonself theory of immunity and the self/nonself vocabulary have been criticized, but remain very influential.
What property of T cells caused modification of CST?
the complex "two-signal" activation