Tagle was born on June 21, 1957, the eldest child of devout Catholic parents, Manuel Topacio Tagle, an ethnic Tagalog and his Chinese Filipino wife, Milagros Gokim, who previously worked for Equitable PCI Bank.  Tagle's paternal grandfather, Florencio, came from Imus, Cavite; the Tagle family were from the Hispanic, lowland Christian aristocracy known as the Principalia, which were the elite prior to the 1896 Philippine Revolution. Florencio was injured by a bomb explosion during the Second World War; Tagle's grandmother made a living by running a local diner.  After attending elementary and high school at Saint Andrew's School in Paranaque, he was influenced by priest friends to enter the Jesuit San Jose Seminary, which sent him for studies at the Jesuit Ateneo de Manila University.  Tagle earned a Bachelor of Arts degree in pre-divinity from Ateneo in 1977 and then a Master of Arts in theology at its Loyola School of Theology. Tagle earned his Doctorate in Sacred Theology at the Catholic University of America from 1987 to 1991. He wrote his dissertation under the direction of Joseph A. Komonchak on the development of the concept of episcopal collegiality at the Second Vatican Council and the influence of Pope Paul VI. Tagle also attended doctrinal courses at the Institute of Pope Paul VI University. In Komonchak's estimation, Tagle was "one of the best students I had in over 40 years of teaching" and "could have become the best theologian in the Philippines, or even in all of Asia" had he not been appointed bishop. Tagle has received honorary degrees from Catholic Theological Union  and La Salle University.

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